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1

Treatment Option Overview (Hairy Cell Leukemia)  

MedlinePLUS

... types of treatment for patients with hairy cell leukemia. Different types of treatment are available for patients with hairy cell leukemia . Some treatments are standard (the currently used treatment), ...

2

Treatment Options for Hairy Cell Leukemia  

MedlinePLUS

... attack specific cancer cells without harming normal cells. Monoclonal antibody therapy is a type of targeted therapy used to treat hairy cell leukemia. Monoclonal antibody therapy uses antibodies made in the laboratory from a ...

3

Eliminating Hairy Cell Leukemia Minimal Residual Disease  

Cancer.gov

In this trial, patients with hairy cell leukemia who have disease-related symptoms that require treatment, and who have not been treated or have had only one prior treatment with cladribine, will be randomly assigned to receive cladribine with either concurrent rituximab or rituximab at least 6 months after completing cladribine therapy.

4

Hairy cell leukemia accompanied by Evans syndrome.  

PubMed

We report a case of Western type hairy cell leukemia (HCL), a very rare leukemia in Japan. In this malignancy, leukemic cells in a peripheral blood film may be missed due in part to accompanying pancytopenia and in part to loss of typical cytoplasmic projections if prepared in a conventional Japanese way using forced air-drying. Our present patient also had a variety of autoantibodies and the clinical picture was primarily that of Evans syndrome (ES), suggesting disturbed immune responses associated with the HCL. Although HCL accompanied by either AIHA or ITP has been reported, the occurrence of ES in HCL is extremely rare. PMID:24850460

Ebara, Shigeyuki; Kagosima, Mizuho; Marumo, Mikio; Ito, Yasusi; Tatumi, Eiji; Mitsutani, Susumu

2014-04-01

5

75 FR 54496 - Diseases Associated With Exposure to Certain Herbicide Agents (Hairy Cell Leukemia and Other...  

Federal Register 2010, 2011, 2012, 2013, 2014

...With Exposure to Certain Herbicide Agents (Hairy Cell Leukemia and Other Chronic B-Cell Leukemias, Parkinson's Disease and Ischemic...an amendment to 38 CFR 3.309 to add hairy cell leukemia and other chronic B-cell...

2010-09-08

6

Leukemia - B-Cell Prolymphocytic Leukemia and Hairy Cell Leukemia  

MedlinePLUS

... of leukemia in adults: Acute lymphocytic leukemia (ALL) Chronic lymphocytic leukemia (CLL) Acute myeloid leukemia (AML) Chronic myeloid leukemia (CML) ... of leukemia may occur by itself, together with CLL , or CLL may turn into PLL. PLL tends ...

7

General Information about Hairy Cell Leukemia  

MedlinePLUS

... is made mostly of fat. Leukemia may affect red blood cells, white blood cells, and platelets. Normally, ... one of three types of mature blood cells: Red blood cells that carry oxygen and other substances ...

8

Immunotoxin Therapy for Treatment-Resistant Hairy Cell Leukemia  

Cancer.gov

In this trial, patients with hairy cell leukemia who have relapsed multiple times or not responded to prior chemotherapy will be treated with an experimental immunotoxin called moxetumomab pasudotox given intravenously on days 1, 3, and 5 of 28-day cycles.

9

Treating Multiply Relapsed or Refractory Hairy Cell Leukemia  

Cancer.gov

In this trial, patients with hairy cell leukemia who have not responded to initial chemotherapy followed by second-line treatment with rituximab, or who have relapsed following two courses of chemotherapy, will be randomly assigned to receive rituximab combined with either pentostatin or bendamustine.

10

Hairy cell leukemia: clinical features and therapeutic advances  

Microsoft Academic Search

Hairy cell leukemia (HCL) is a rare chronic lymphoproliferative disorder which has been extensively studied over the past decade. Much has been learned regarding the diagnosis, natural history, biology, and treatment of this unique neoplasm. The disease most commonly affects middle aged men and characteristic clinical features include splenomegaly, cytopenias, and usually the presence in the peripheral blood of distinctive

Barry C. Lembersky; Harvey M. Golomb

1987-01-01

11

Marked Retroperitoneal Lymphadenopathy in Hairy Cell Leukemia: A Case Report  

PubMed Central

Hairy cell leukemia (HCL) is uncommonly associated with lymphadenopathy, while retroperitoneal lymphadenopathy is extremely uncommon. We report on a patient with a 12-year history of HCL who developed painless jaundice and ascites, accompanied by positional discomfort with persistent nausea. Computed tomography examination revealed 2 large retroperitoneal masses, which at autopsy consisted of HCL with focally intermixed pancreatic and peripancreatic tissue. Lymphadenopathy was not identified above the diaphragm or below the aortic bifurcation. No vasculitis or an unusual HCL histology was identified. As previous reports, our findings suggest that HCL with massive lymphadenopathy has a specific site predilection, but it is not necessarily accompanied by vasculitis or an unusual histology. PMID:24163667

Shackelford, R.E.; Heldmann, M.; Eskandari, F.; Joshi, N.; Browning, J.; Maxwell, N.; Coteligam, J.

2013-01-01

12

Two Cases of Q-Fever in Hairy Cell Leukemia  

PubMed Central

Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder accounting for about 2% of all leukemias. The clinical course is indolent, however HCL patients are particularly susceptible to infections. Here we report two cases of Q-fever as first manifestation of disease in two patients affected by HCL. Both patients described in this report showed an unusually sluggish clinical response to the antibiotic treatment with ciprofloxacin probably because of the marked immunodeficiency. However, treatment of HCL with cladribine administered soon after the resolution of QF pneumonitis was uneventful and led to a complete remission in both cases. Most probably the association of Coxiella burnetii (CB) infection and HCL that we observed in two patients is due to chance. However, a hairy cell resembling transformation of freshly isolated human peripheral blood lymphocytes upon CB has been showed. We think that the possibility of CB infection in febrile HCL patient should be always taken in mind, especially in endemic areas. In addition the potential for such infections to become chronic in HCL patients should not be overlooked and the reporting of further cases should be encouraged. PMID:25180111

Iannitto, Emilio; Tick, Lidwine W.; Arents, Nicolaas L. A.; Kuijper, Philip H.; Nijziel, Marten R.

2014-01-01

13

Transformation of hairy cell leukemia to EBV genome-containing aggressive B cell lymphoma.  

PubMed

Hairy cell leukemia is a preplasmacytic B cell leukemia which is not EBV associated, although elevated titers of Epstein-Barr virus (EBV) antibodies have been seen in this leukemia and chronic lymphocytic leukemia. Hairy cells are not readily susceptible to EBV infection in vitro, even though they are EBV receptor-positive B cells. We have observed a 59-year-old patient who after 9 years of hairy cell leukemia developed a well-differentiated IgG-kappa monoclonal B cell lymphoma without further evidence of hairy cell leukemia. Pathologically, the lymphoma showed plasmacytic differentiation, and in the patient's serum, a 2 g/dl monoclonal IgG-kappa component was present. DNA extracted from the lymphomatous lymph node hybridized with DNA fragments of a reiterated sequence of EBV, IR1. The transformation, with no chemotherapy involved, from a preplasmacytic leukemia into a lymphoplasmacytic lymphoma with monoclonal gammopathy may be related to the entry of EBV into these cells. Studies at the molecular level may help understand mechanisms of malignant transformation or interconversion in lymphoproliferative disorders of the B cell type. PMID:2823016

Huang, A T; Silverstein, L; Gonias, S L; Rundles, R W; Raab-Traub, N

1987-04-01

14

Hairy cell leukemia: short review, today's recommendations and outlook  

PubMed Central

Hairy cell leukemia (HCL) is part of the low-grade non-Hodgkin lymphoma family and represents approximately 2% of all leukemias. Treatment with splenectomy and interferon-? historically belonged to the first steps of therapeutic options, achieving partial responses/remissions (PR) in most cases with a median survival between 4 and 6 years in the 1980s. The introduction of the purine analogs (PA) pentostatin and cladribine made HCL a well-treatable disease: overall complete response rates (CRR) range from 76 to 98%, with a median disease-free survival (DFS) of 16 years a normal lifespan can be reached and HCL-related deaths are rare. However, insufficient response to PA with poorer prognosis and relapse rates of 30–40% after 5–10 years of follow-up may require alternative strategies. Minimal residual disease can be detected by additional examinations of bone marrow specimens after treatment with PA. The use of immunotherapeutic monoclonal antibodies (mAB) like rituximab as a single agent or in combination with a PA or more recently clinical trials with recombinant immunotoxins (RIT) show promising results to restrict these problems. Recently, the identification of the possible disease-defining BRAF V600E mutation may allow the development of new therapeutic targets. PMID:24531447

Maevis, V; Mey, U; Schmidt-Wolf, G; Schmidt-Wolf, I G H

2014-01-01

15

Cladribine underdosing in hairy-cell leukemia: a cause for apparent response failure.  

PubMed

While chemotherapy overdose is often readily discovered, underdosing errors are seldom appreciated. We report two patients with hairy-cell leukemia who apparently failed to respond to cladribine administered by continuous portable pump infusion. It was determined that both patients received one-seventh of the prescribed dose, although the orders were written correctly. The errors resulted in the administration of 1 day's dose over 1 week. The use of 7-day portable pump infusion therapy for cladribine can be associated with misdosing, and is an occult cause of apparent failure to respond in hairy-cell leukemia. PMID:11999571

Golde, David W; Jakubowiak, Andrzej; Caggiano, Janine; Heaney, Mark L

2002-02-01

16

[A predisposing clinical condition for disseminated tuberculosis: hairy cell leukemia].  

PubMed

Hairy cell leukemia (HCL), a rare and slow-progressive B-cell lymphoproliferative disease, enhances predisposition to infectious complications, especially to disseminated mycobacterial infections. Although the association between HCL and mycobacterial disease has been established, disseminated Mycobacterium tuberculosis infection has been reported only in a few case series. In this report, a disseminated tuberculosis (TB) case who had been diagnosed as HCL with histopathologic examination of the bone marrow after being investigated for the etiology of fever of unknown origin, was presented. A 56-year-old male patient who was admitted to our clinic with the complaints of three weeks' duration fever, chills, night sweats and cough was hospitalized. On physical examination, the body temperature of the patient who appeared very ill, was 39°C. Dispersed macular rash that turned pale when pressure was applied, was detected on the legs, arms and back. There were no signs of peripheral lymphadenopathy, hepatomegaly or splenomegaly. Laboratory results revealed haemoglobin 10 g/dl, white blood cell count 1000/mm3, thrombocytes 143.000/mm3, erythrocyte sedimentation rate 41 mm/h, CRP 200 mg/L, uric acid 9.5 mg/dl, AST 118 IU/L, ALT 102 IU/L and LDH 429 IU/L. Thorax computed tomography showed mediastinal and bilateral hilary lymphadenopathy. Although preliminary diagnosis was lymphoma, examination of acid-fast bacilli in three days sequential sputum samples and sputum culture for the growth of mycobacteria (Bactec MGIT 960 TB system, Becton Dickinson, Md) were performed to rule out miliary TB. Blood cultures were also performed with non-radiometric fully automated TB hemoculture bottles (Bactec TB, Becton Dickinson, Md). Sputum cultures yielded no mycobacterial growth, however M.tuberculosis growth was detected in blood culture on the 27th day of inoculation. Bone marrow biopsy revealed HCL. However the patient died on the 14th day of hospitalization. In conclusion, disseminated tuberculosis should be considered for differentional diagnosis in patients with HCL or similar hematologic malignancies since TB is endemic in Turkey. PMID:23621735

Arslan, Ferhat; Bat?rel, Ay?e; Ozer, Serdar; Ca?an Akta?, Sabahat

2013-04-01

17

Rearrangement and expression of immunoglobulin genes and expression of Tac antigen in hairy cell leukemia.  

PubMed Central

The origin and exact stage of differentiation of the neoplastic cells that comprise hairy cell leukemia have remained uncertain. As Ig heavy and light chain genes must both undergo a DNA rearrangement during B-cell development but rarely do so within other hematopoietic lineages, we examined these genes in this leukemia. The neoplastic cells of all eight cases demonstrated rearranged heavy and light chain genes and, in two cases examined, contained the corresponding mRNA for heavy and light chain Ig. Consistent with this B-cell genotype, all cases displayed cell surface HLA-DR and B-cell-associated antigens. Unexpectedly, all cases demonstrated cell surface Tac antigen, which previously had been restricted predominantly to select T-cell malignancies and activated T cells. Prior studies suggested that the anti-Tac monoclonal antibody recognized a peptide associated with the binding of interleukin 2 (T-cell growth factor) in such T cells. Immunoprecipitation with anti-Tac and NaDodSO4/polyacrylamide gel electrophoresis revealed an antigen on leukemic hairy cells with a Mr of 53,000-57,000, identical in size to the receptor on activated T cells. This apparent biphenotypic status might reflect a transformation-associated expression of the Tac antigen in this leukemia. Alternatively, hairy cell leukemia may be a malignancy of a unique stage of normal B-cell differentiation in which the Tac antigen is expressed. Images PMID:6192435

Korsmeyer, S J; Greene, W C; Cossman, J; Hsu, S M; Jensen, J P; Neckers, L M; Marshall, S L; Bakhshi, A; Depper, J M; Leonard, W J; Jaffe, E S; Waldmann, T A

1983-01-01

18

Leukemic meningitis in a patient with hairy cell leukemia. A case report  

SciTech Connect

Central nervous system involvement has not previously been described in patients with hairy cell leukemia (HCL). A patient is reported who presented with meningeal involvement as his initial symptom of HCL. Diagnosis was established by morphologic and cytochemical studies of his cerebrospinal fluid (CSF) and bone marrow. Treatment with whole-brain irradiation and intrathecal chemotherapy was successful in clearing leukemic cells from the CSF with resolution of symptoms.

Wolfe, D.W.; Scopelliti, J.A.; Boselli, B.D.

1984-09-15

19

Isolated Splenic Mycobacterial Disease: A Cause of Persistent Fever in a Hairy Cell Leukemia Patient.  

PubMed

We describe a 69-year-old male patient who was referred for the investigation of long-lasting fever, anemia and neutropenia. Hairy cell leukemia was diagnosed and treated successfully. However, fever persisted despite thorough investigation and use of broad-spectrum antibiotics. Four months after the initial diagnosis, the patient underwent explorative laparotomy and splenectomy. Spleen biopsy revealed multiple necrotizing mycobacterial granulomata while the patient's fever disappeared permanently. Isolated splenic mycobacterial disease is very rare. This case report emphasizes that investigation of chronic fever in hairy cell leukemia requires a high level of clinical suspicion. Early diagnostic procedures for evidence of atypical mycobacterial infection should be considered. When everything else fails, surgery can be helpful in selected cases. PMID:21060695

Papadopoulos, Vassilios; Kartsios, Charalambos; Spyrou, Anastassia; Loukidis, Kostas; Miyakis, Spyridon; Pervana, Stavroula; Makridis, Charalambos; Kioumi, Anna; Korantzis, Ioannis

2010-01-01

20

Isolated Splenic Mycobacterial Disease: A Cause of Persistent Fever in a Hairy Cell Leukemia Patient  

PubMed Central

We describe a 69-year-old male patient who was referred for the investigation of long-lasting fever, anemia and neutropenia. Hairy cell leukemia was diagnosed and treated successfully. However, fever persisted despite thorough investigation and use of broad-spectrum antibiotics. Four months after the initial diagnosis, the patient underwent explorative laparotomy and splenectomy. Spleen biopsy revealed multiple necrotizing mycobacterial granulomata while the patient's fever disappeared permanently. Isolated splenic mycobacterial disease is very rare. This case report emphasizes that investigation of chronic fever in hairy cell leukemia requires a high level of clinical suspicion. Early diagnostic procedures for evidence of atypical mycobacterial infection should be considered. When everything else fails, surgery can be helpful in selected cases. PMID:21060695

Papadopoulos, Vassilios; Kartsios, Charalambos; Spyrou, Anastassia; Loukidis, Kostas; Miyakis, Spyridon; Pervana, Stavroula; Makridis, Charalambos; Kioumi, Anna; Korantzis, Ioannis

2010-01-01

21

Unusual Soft Tissue Infiltrates With 18F-FDG Uptake in a Patient With Hairy Cell Leukemia.  

PubMed

Hairy cell leukemia (HCL) is an uncommon B-cell lymphoproliferative disorder, representing approximately 2% of leukemias. Diagnostic features include pancytopenia, splenomegaly, bone marrow reticulin fibrosis, and circulating hairy cells. Less commonly, there may be involvement of the liver and lymph nodes. We present a case of a 53-year-old man with HCL who was found to have soft tissue masses within the mediastinum and neck during pretreatment workup. An F-FDG PET/CT scan was requested to assess these lesions before treatment. These extensive infiltrates were FDG avid, and core biopsy of the mediastinal tissue was undertaken. Results were consistent with HCL. PMID:25783506

Gibson, Glenna; Lai, Jerome; Thomas, Paul

2015-05-01

22

CD5+ Immunophenotype in the Bone Marrow but Not in the Peripheral Blood in a Patient with Hairy Cell Leukemia  

Microsoft Academic Search

We report the case of a patient with rare CD5+ hairy cell leukemia, which was unusual, as there was also a discrepancy between the bone marrow and peripheral blood immunophenotypes. We propose that some degree of maturation within the malignant clone and the predominance of more mature CD5– hairy cells in the peripheral blood can explain this observation. The patient

Lydia Usha; Basil Bradlow; Wendy Stock; Leonidas C. Platanias

2000-01-01

23

Hairy cell leukemia in kidney transplantation: lesson from a rare disorder.  

PubMed

We report here on the diagnosis and successful treatment of a case of hairy cell leukemia (HCL) that arose 15 years after kidney transplantation in a 51-year-old patient. As soon as the diagnosis was made, HCL was treated with 2-CDA, obtaining complete hematological remission. Immunosuppression with the calcineurin inhibitor cyclosporin was maintained, and the graft was preserved. In kidney transplant recipients supported with immunosuppressive drugs, post-transplant lymphoproliferative diseases (PTLDs) are frequent and typically related to immunosuppression via a loss of control of infectious/EBV-related proliferative stimuli. To date, HCL has not been considered among PTLDs. Recently, however, the oncogenic mutation V600E of the BRAF protein kinase has been found to be a hallmark of HCL, and calcineurin inhibitors have been shown to interfere with signaling downstream of V600E BRAF early on by counteracting senescence-associated mechanisms that protect against the oncogenic potential of the mutated kinase. Such a biochemical link between the oncogene-dependent signaling and calcineurin inhibitor activities suggests that HCL in transplanted patients might be a peculiar type of PTLD based on the presence of a specific mutation. This mechanism might also be involved in other neoplasias bearing the same or similar mutations, such as melanoma and non-melanoma skin cancer. PMID:23927433

Vinante, Fabrizio; Tomei, Paola; Zaza, Gianluigi; Zamò, Alberto; Lupo, Antonio

2013-01-01

24

Is it really possible to cure hairy cell leukemia patients only with frontline therapy?  

PubMed

Hairy cell leukemia (HCL) patients could have an excellent prognosis with adequate treatment. Treatments are not generally curative but are extremely effective in inducing long-lasting clinical remissions. An observational retrospective study was conducted on a single-center registry of 144 patients with a median follow-up of 11.5 years, focusing on long-lasting continuous first complete remissions (CR) wondering if patients can be cured only with front-line approach. CR for more than 5 years after first-line therapy were found in 22.2 % cases. The median duration of response was 9.8 years, while for relapsed patients, the first response had a median duration of 2.4 years. Three different subsets of long-lasting first CR were identified: 15 patients are between 5 and 10 years with a median duration of CR of 6.5 years; 7 patients are between 10 and 15 years with a median duration of CR of 12.3 years; and 10 patients present a follow-up superior to 15 years with a median duration of CR of 20.0 years. There is a need for continuous study in this field to better define the optimal therapeutic regimen and, in particular, the biological issues since at least 20-25 % of HCL patients can be cured with only one treatment. PMID:24752417

Zinzani, Pier Luigi; Stefoni, Vittorio; Broccoli, Alessandro; Pellegrini, Cinzia; Gandolfi, Letizia; Casadei, Beatrice; Maglie, Roberto; Pileri, Stefano; Argnani, Lisa

2014-09-01

25

BRAF inhibitors reverse the unique molecular signature and phenotype of hairy cell leukemia and exert potent antileukemic activity  

PubMed Central

Hairy cell leukemia (HCL) shows unique clinicopathological and biological features. HCL responds well to purine analogs but relapses are frequent and novel therapies are required. BRAF-V600E is the key driver mutation in HCL and distinguishes it from other B-cell lymphomas, including HCL-like leukemias/lymphomas (HCL-variant and splenic marginal zone lymphoma). The kinase-activating BRAF-V600E mutation also represents an ideal therapeutic target in HCL. Here, we investigated the biological and therapeutic importance of the activated BRAF–mitogen-activated protein kinase kinase (MEK)–extracellular signal-regulated kinase (ERK) pathway in HCL by exposing in vitro primary leukemic cells purified from 26 patients to clinically available BRAF (vemurafenib; dabrafenib) or MEK (trametinib) inhibitors. Results were validated in vivo in samples from vemurafenib-treated HCL patients within a phase 2 clinical trial. BRAF and MEK inhibitors caused, specifically in HCL (but not HCL-like) cells, marked MEK/ERK dephosphorylation, silencing of the BRAF-MEK-ERK pathway transcriptional output, loss of the HCL-specific gene expression signature, downregulation of the HCL markers CD25, tartrate-resistant acid phosphatase, and cyclin D1, smoothening of leukemic cellshairy surface, and, eventually, apoptosis. Apoptosis was partially blunted by coculture with bone marrow stromal cells antagonizing MEK-ERK dephosphorylation. This protective effect could be counteracted by combined BRAF and MEK inhibition. Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL. PMID:25480661

Pettirossi, Valentina; Santi, Alessia; Imperi, Elisa; Russo, Guido; Pucciarini, Alessandra; Bigerna, Barbara; Schiavoni, Gianluca; Fortini, Elisabetta; Spanhol-Rosseto, Ariele; Sportoletti, Paolo; Mannucci, Roberta; Martelli, Maria Paola; Klein-Hitpass, Ludger; Falini, Brunangelo

2015-01-01

26

Application of a BRAF V600E mutation-specific antibody for the diagnosis of hairy cell leukemia.  

PubMed

In recent times BRAF V600E mutations have emerged as a genetic hallmark of hairy cell leukemia (HCL). This specific point mutation is present in virtually all cases of HCL but is exceedingly rare in other peripheral B-cell neoplasms. In this study we investigated the application of a BRAF V600E mutation-specific antibody (clone VE1) to differentiate HCL from HCL mimics, such as HCL variant and splenic marginal zone lymphoma. A total of 52 routinely processed formalin-fixed paraffin-embedded tissue specimens were investigated (bone marrow, n=46; spleen, n=6) for expression of V600E-mutated BRAF protein. All 32 cases of HCL were scored positive, and all non-HCL cases were scored negative. In 28 of 30 HCL cases the presence of a BRAF V600E mutation could be confirmed by direct sequencing, whereas no BRAF mutations were detected among 20 HCL mimics. We further screened 228 mature B-cell neoplasms with VE1 and detected 1 positive case of chronic lymphocytic leukemia. Sequencing confirmed the presence of a BRAF V600E mutation. In conclusion, we demonstrate that VE1 immunohistochemistry can be used to reliably differentiate HCL from HCL-mimicking entities. This on-slide technique might be particularly helpful in interpreting challenging biopsies with low tumor content. PMID:22531170

Andrulis, Mindaugas; Penzel, Roland; Weichert, Wilko; von Deimling, Andreas; Capper, David

2012-12-01

27

A New Subtype of Human T-Cell Leukemia Virus (HTLV-II) Associated with a T-Cell Variant of Hairy Cell Leukemia  

Microsoft Academic Search

Human T-cell leukemia virus (HTLV) is a human type-C RNA tumor virus (retrovirus) previously identified in and isolated from several patients with T-cell leukemias or lymphomas. The known virus isolates from the United States and Japan are closely related and are found in adults with an acute malignancy of mature T cells. A related retrovirus has been found in a

V. S. Kalyanaraman; M. G. Sarngadharan; Marjorie Robert-Guroff; Isao Miyoshi; Douglas Blayney; David Golde; Robert C. Gallo

1982-01-01

28

Hairy cell leukemia-associated antigen LeuM5 (CD11c) is preferentially expressed by benign activated and neoplastic CD8 T cells.  

PubMed Central

LeuM5 antigen (CD11c, p150.95) expression, widely used as an immunodiagnostic marker for B-cell hairy cell leukemia, was examined on benign, normal peripheral blood T cells before and after stimulation in vitro with phytohemagglutinin and on a large, diverse panel of 73 T-cell neoplasms. Resting T cells lacked LeuM5. Intracytoplasmic LeuM5 was detectable at 3 to 4 days and surface membrane LeuM5 was detectable continuously between 5 and 17 days on greater than or equal to 20% CD3 cells (maximum, 42% CD3 cells at 10 days) after activation. Two-color flow cytometric analysis of the activated T cells demonstrated that a maximum of 60% CD8 but only 25% CD4 cells expressed LeuM5; the mean percentage of LeuM5+ CD8 cells was 44% compared with 12% LeuM5+ CD4 cells. A variable proportion of the neoplastic T cells in 19 of 73 (26%) T-cell neoplasms were LeuM5+. Twelve of 18 CD4-CD8+ (67%) but only 5 of 40 CD4+ CD8- T-cell neoplasms expressed LeuM5. These studies demonstrate that the LeuM5 antigen is 1) expressed in association with T-cell activation, 2) preferentially expressed by activated CD8 cells, and 3) variably expressed by neoplastic T cells, but particularly by those exhibiting the CD4- CD8+ phenotype. Images Figure 1 PMID:2105060

Chadburn, A.; Inghirami, G.; Knowles, D. M.

1990-01-01

29

Phospho-ERK(THR202/Tyr214) is overexpressed in hairy cell leukemia and is a useful diagnostic marker in bone marrow trephine sections.  

PubMed

BRAF V600E mutations are present in virtually all cases of hairy cell leukemia (HCL). We hypothesized that detection of phospho-ERK (pERK) in tissue sections may be a useful marker for diagnosis of HCL. pERK/CD20 double immunostaining was performed on 90 formalin-fixed bone marrow trephine samples affected with small B-cell lymphoproliferative disorders, including 28 cases of HCL. pERK staining was observed in all 28 cases of HCL and in 1 of 62 cases of non-HCL B-cell lymphoproliferative disorders. By allele-specific polymerase chain reaction, all 11 cases of HCL with available DNA were positive for BRAF V600E, as was the 1 pERK non-HCL case. The remaining 31 non-HCL cases tested were negative for BRAF V600E. The sensitivity and specificity of pERK for diagnosis of HCL was 100% and 98%, respectively. We conclude that the presence of pERK as detected by immunohistochemical staining is a useful surrogate marker for BRAF V600E in the diagnosis of HCL. PMID:23211289

Warden, Douglas W; Ondrejka, Sarah; Lin, Jeffrey; Durkin, Lisa; Bodo, Juraj; Hsi, Eric D

2013-02-01

30

Concentrations of organochlorines related to titers to Epstein-Barr virus early antigen IgG as risk factors for hairy cell leukemia.  

PubMed Central

Hairy cell leukemia (HCL) is a rare chronic B-cell malignancy that, according to modern classifications, is a subgroup of non-Hodgkin lymphomas (NHLs). A rapid increase in incidence of NHL has been reported in many countries. The reasons for this increase are largely unknown, but exposure to organochlorines has been suggested as a risk factor. Epstein-Barr virus is a human herpesvirus that has been associated with certain subgroups of NHL. In this study, we measured lipid adjusted blood concentrations (in nanogram per gram) of 36 congeners of polychlorinated biphenyls (PCBs), p, p'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), and four subgroups of chlordanes (trans-nonachlor, cis-nonachlor, MC6, and oxychlordane) in incident cases of HCL and controls from the general population. We obtained results on organochlorines and antibodies for 54 cases and 54 controls. Titers of antibodies to the Epstein-Barr early antigen and Epstein-Barr nuclear antigen, measured as P107, were correlated to concentrations of organochlorines to evaluate the possibility of an interaction between these factors in the pathogenesis of HCL. We found no significant difference in lipid-adjusted blood concentrations of total PCBs, p,p'-DDE, HCB, or the sum of the chlordanes between cases and controls. Titers of antibodies to Epstein-Barr early antigen IgG [Greater and equal to] 40 were correlated to an increased risk for HCL. This risk was further increased in those with a level above the median value of p,p'-DDE, HCB, or the sum of the chlordanes, suggesting an interaction between Epstein-Barr virus and a higher concentration of these chemicals. We also found increased risk for the sum of immunotoxic PCB group. PMID:10811571

Nordström, M; Hardell, L; Lindström, G; Wingfors, H; Hardell, K; Linde, A

2000-01-01

31

Regulation of hairy-cell survival through constitutive activation of mitogen-activated protein kinase pathways  

Microsoft Academic Search

The hairy cells (HCs) of hairy-cell leukemia are intrinsically activated mature clonal B cells. The aims of this study were to gain further insights into the nature of this activation and to assess its importance for the prolonged HC survival in this chronic disease. We show that HCs contain phosphorylated\\/activated p38 MAPK, JNK and ERK1\\/ERK2 (ERK1\\/2). PKC inhibitors increased the

Aura S Kamiguti; Robert J Harris; Joseph R Slupsky; Peter K Baker; John C Cawley; Mirko Zuzel

2003-01-01

32

Cellular Immunotherapy Following Cyclophosphamide in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia or B-Cell Prolymphocytic Leukemia  

ClinicalTrials.gov

Post-transplant Lymphoproliferative Disorder; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Waldenström Macroglobulinemia

2015-01-29

33

Leukemia -- Chronic T-Cell Lymphocytic  

MedlinePLUS

... Lymphocytic: Overview Print to PDF Leukemia - Chronic T-Cell Lymphocytic: Overview Approved by the Cancer.Net Editorial ... leukemia (AML) Chronic myeloid leukemia (CML) About T-cell leukemia There are also less common types of ...

34

Childhood Leukemia--A Look at the Past, the Present and the Future.  

ERIC Educational Resources Information Center

Provides an overview of childhood leukemia. The causes, the survival period, different types (acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and hairy cell leukemia), symptoms, treatment, side effects of treatment (including learning problems), and the expected future direction of…

Findeisen, Regina; Barber, William H.

1997-01-01

35

Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia  

ClinicalTrials.gov

Adult B Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone Lymphoma; Post-Transplant Lymphoproliferative Disorder; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

2014-12-30

36

PLASMA CELL LEUKEMIA  

PubMed Central

Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathologic entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (? 20%) and absolute number (? 2 × 10 9/L) of plasma cells in the peripheral blood. It is proposed that the thresholds for diagnosis be reexamined and consensus recommendations are made for diagnosis, as well as, response and progression criteria. Induction therapy needs to begin promptly and have high clinical activity leading to rapid disease control in an effort to minimize the risk of early death. Intensive chemotherapy regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem-cell transplantation (HDT/ASCT) if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding of the pathogenesis of PCL. PMID:23288300

de Larrea, Carlos Fernandez; Kyle, Robert A.; Durie, Brian GM; Ludwig, Heinz; Usmani, Saad; Vesole, David H.; Hajek, Roman; Miguel, Jésus San; Sezer, Orhan; Sonneveld, Pieter; Kumar, Shaji K.; Mahindra, Anuj; Comenzo, Ray; Palumbo, Antonio; Mazumber, Amitabha; Anderson, Kenneth C.; Richardson, Paul G.; Badros, Ashraf Z.; Caers, Jo; Cavo, Michele; LeLeu, Xavier; Dimopoulos, Meletios A.; Chim, CS; Schots, Rik; Noeul, Amara; Fantl, Dorotea; Mellqvist, Ulf-Henrik; Landgren, Ola; Chanan-Khan, Asher; Moreau, Philippe; Fonseca, Rafael; Merlini, Giampaolo; Lahuerta, JJ; Bladé, Joan; Orlowski, Robert Z.; Shah, Jatin J.

2014-01-01

37

MK2206 in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Leukemia  

ClinicalTrials.gov

Accelerated Phase Chronic Myelogenous Leukemia; Acute Leukemias of Ambiguous Lineage; Acute Myeloid Leukemia/Transient Myeloproliferative Disorder; Acute Undifferentiated Leukemia; Aggressive NK-cell Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myeloid/NK-cell Acute Leukemia; Noncutaneous Extranodal Lymphoma; Post-transplant Lymphoproliferative Disorder; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

2014-04-28

38

Leukemia  

MedlinePLUS

Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

39

Sugar utilization and invertase activity in hairy-root and cell-suspension cultures of Symphytum officinale  

Microsoft Academic Search

Incomplete consumption of sugars can lead to limited growth of hairy roots. To shed light on this phenomenon, growth, sugar\\u000a consumption, and invertase activity were examined in hairy-root batch cultures of Symphytum officinale L. and in reference cell-suspension cultures of the same species. Sucrose was supplied as sole carbon source. In the hairy-root\\u000a cultures, sucrose concentration decreased gradually during growth,

Nurit Shimon-Kerner; David Mills; Jose C. Merchuk

2000-01-01

40

Leukemia among participants in military maneuvers at a nuclear bomb test. [Plumbbob Project  

Microsoft Academic Search

Preliminary studies indicate that nine cases of leukemia have occurred among 3224 men who participated in military maneuvers during the 1957 nuclear test explosion Smoky. This represents a significant increase over the expected incidence of 3.5 cases. They included four cases of acute myelocytic leukemia, three of chronic myelocytic leukemia, and one each of hairy cell and acute lymphocytic leukemia.

G. G. Caldwell; D. B. Kelley; C. W. Jr. Heath

1980-01-01

41

Leukemia  

MedlinePLUS

Leukemia is a type of blood cancer that begins in the bone marrow. Bone marrow is the ... bones, where blood cells are produced. The term leukemia means white blood. White blood cells (leukocytes) are ...

42

A flow cell reactor for the study of growth kinetics of single hairy roots  

Microsoft Academic Search

A flow cell reactor designed for the study of growth and branching of individual roots under defined fluid flow conditions is described and preliminary results with the hairy root clone Tagetes erecta T3 are presented. Observations of root growth in this reactor may help to formulate and verify mathematical models root growth kinetics.

Jennifer Flint-Wandel; Martin Hjortso

1993-01-01

43

ADULT T CELL LEUKEMIA LYMPHOMA  

PubMed Central

Adult T cell leukemia lymphoma (ATLL) is a CD4+ lymphoproliferative malignancy resulting from human T-cell leukemia virus type 1 (HTLV1) infection. It includes differing clinical forms classified as smoldering, chronic, lymphomatous, and acute ATLL. The Tax protein of HTLV-1 has been implicated as a viral oncoprotein which enhances virus replication and alters cellular gene expression, including activation of nuclear factor kappa B (NF kB), to result in lymphoid transformation. Chemotherapy for ATLL has had limited efficacy with median survivals of about 1 yr. Antiviral therapy employing zidovudine and interferon has shown promising results, as have antibody-based therapies to the interleukin 2 (IL2) receptor. Novel approaches employ a combination of chemo/antiretroviral therapy, hematopoietic stem cell transplantation, or inhibitors of NF kB activation. PMID:15353320

Ratner, Lee

2009-01-01

44

Hairy Baskets” Associated with Degenerative Purkinje Cell Changes in Essential Tremor  

PubMed Central

Essential tremor (ET) is one of the most common neurological diseases. Increased numbers of torpedoes and Purkinje cell loss have been documented in the brains of patients with ET. We recently observed a dense and tangled appearance (“hairiness”) of the basket cell axonal plexuses that surround Purkinje cell soma in Bielschowsky preparations of cerebellar cortex in ET brains. Here, we assessed basket cellhairiness” in 37 ET (32 cerebellar ET; 5 Lewy body variant ET [LBVET]), 21 non-disease control, and 48 disease control brains using a semiquantitative scale. In 8 cerebellar ET cases (25%) there were high basket scores (rating = 3), whereas no LBVET, 1 non-disease control (4.8%) and 2 diseased controls (4.2%) had high basket scores (p = 0.001). The hairy basket scores correlated with numbers of torpedoes (p < 0.001) and inversely with numbers of Purkinje cells (p = 0.06). Axonal plexus density obtained by image analysis of basket cell processes traced from digitized images was higher in ET than in non-diseased control cases (p = 0.016). Closely spaced sites of synaptic contact between basket cell processes and Purkinje cells were identified by electron microscopy in ET cases. These data indicate that structural changes are not restricted to Purkinje cells in ET and that other neurons within their functional network may be involved in its pathogenesis. PMID:20142764

Erickson-Davis, Cordelia; Faust, Phyllis L.; Vonsattel, Jean-Paul G.; Gupta, Sachin; Honig, Lawrence S.; Louis, Elan D.

2010-01-01

45

"Hairy baskets" associated with degenerative Purkinje cell changes in essential tremor.  

PubMed

Essential tremor (ET) is one of the most common neurologic diseases. Increased numbers of torpedoes and Purkinje cell (PC) loss have been documented in the brains of patients with ET. We recently observed a dense and tangled appearance ("hairiness") of the basket cell axonal plexuses that surround PC soma in Bielschowsky preparations of cerebellar cortex in ET brains. Here, we assessed basket cell "hairiness" in 37 ET (32 cerebellar ET; 5 Lewy body variant ET), 21 nondisease control, and 48 disease control brains using a semiquantitative scale. In 8 cerebellar ET cases (25%), there were high basket scores (rating = 3), whereas no Lewy body variant ET, 1 nondisease control (4.8%), and 2 diseased controls (4.2%) had high basket scores (p = 0.001). The hairy basket scores correlated with numbers of torpedoes (p < 0.001) and inversely with numbers of PCs (p = 0.06). Axonal plexus density obtained by image analysis of basket cell processes traced from digitized images was higher in ET than in nondiseased control cases (p = 0.016). Closely spaced sites of synaptic contact between basket cell processes and PCs were identified by electron microscopy in ET cases. These data indicate that structural changes are not restricted to PCs in ET, and that other neurons within their functional network may be involved in its pathogenesis. PMID:20142764

Erickson-Davis, Cordelia R; Faust, Phyllis L; Vonsattel, Jean-Paul G; Gupta, Sachin; Honig, Lawrence S; Louis, Elan D

2010-03-01

46

Leukemia  

MedlinePLUS

... two are acute, meaning they get worse quickly. chronic lymphocytic leukemia chronic myeloid leukemia acute myeloid leukemia acute lymphocytic leukemia Chronic and Acute Leukemia Chronic lymphocytic leukemia, chronic myeloid leukemia, and acute myeloid leukemia are ...

47

Selective T-Cell Depletion to Reduce GVHD (Patients) Receiving Stem Cell Tx to Treat Leukemia, Lymphoma or MDS  

ClinicalTrials.gov

Graft vs Host Disease; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myelomonocytic, Chronic; Leukemia, Lymphocytic; Lymphoma; Lymphoma, Mantle-cell; Lymphoma, Non-Hodgkin; Hodgkin Disease

2011-12-09

48

Effects of cycloartane saponins from hairy roots of Astragalus membranaceus Bge., on human tumor cell targets.  

PubMed

For the first time three different natural compounds, isolated from hairy roots of Astragalus membranaceus, cultivated in airlift bioreactor were tested for their cytotoxic potential and apoptosis induction in a panel of human tumor cell lines. Root cultures, cultivated in bioreactor gave 18.5 g l(-1) dry wt roots with the highest astragaloside production in vitro up to now - 1.64% (astragaloside I), 1.12% (astragaloside II) and 1.08% (astragaloside III). In this manner the production in airlift bioreactor can be used as means of reliable supply of cycloartane saponins to extend the research to human clinical studies. PMID:20060881

Ionkova, I; Momekov, G; Proksch, P

2010-07-01

49

Lenalidomide With or Without Rituximab in Treating Patients With Progressive or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Prolymphocytic Leukemia, or Non-Hodgkin Lymphoma Previously Treated With Donor Stem Cell Transplant  

ClinicalTrials.gov

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

2014-04-03

50

Sensory Cells of the Fish Ear: A Hairy Enigma  

NASA Technical Reports Server (NTRS)

Analysis of the structure of the ears in teleost fishes has led to the tentative suggestion that otolithic endorgans may function differently, in different species. Recently, evidence has demonstrated different 'types' of sensory hair cells can be found in the ears of teleost fishes, and individual hair cell types are found in discrete regions of individual sensory, epithelia. The presence of multiple hair cell types in fishes provides strong support to the hypothesis of regional differences in the responses of individual otolithic sensory epithelia. The finding of hair cell types in fishes that closely resemble those found in amniote vestibular endorgans also suggests that hair cell heterogeneity arose earlier in the evolution of the vertebrate ear than previously thought.

Popper, A. N.; Saidel, W. M.

1995-01-01

51

Coexistent hairy cell leukaemia and hepatosplenic t-cell lymphoma: a case report  

PubMed Central

Background Hairy cell leukaemia (HCL) is a chronic B-cell leukaemia characterized by expansion of neoplastic cells in the spleen, bone marrow and blood. Symptoms of HCL are related to pancytopenia and immune deficiency. Patients with HCL have an increased risk of second malignancy either in a form of synchronous disease or in a form of an increased incidence of a second neoplasm after the treatment of HCL. Hepatosplenic T-cell lymphoma (HSTCL) is a rare form of aggressive extranodal T-cell lymphoma. Its pathogenesis is connected to a chronic immune deficiency status and its coexistence with other neoplasms is practically non-existent. Case We present a case of a 53-year-old female patient suffering from hepatosplenomegaly, peripheral lymphadenopathy and related B symptoms. An excisional biopsy of the enlarged axillary lymph node revealed partial infiltration with CD3+/CD56+/TIA?+?T cell lymphoma. Bone marrow trephine biopsy and flow cytometric immunophenotypization of bone marrow cells and peripheral blood showed presence of two types of neoplastic cells in the peripheral blood and in the bone marrow (composite lymphoma). One of them showed typical morphologic characteristics and immunohistochemical features of HCL, while another one was morphologically and immunophenotypically consistent with the diagnosis of HSTCL, respectively. The patient was treated with multivalent chemotherapy including rituximab but all treatments turned out to be only partially effective. While HCL responded to the treatment, HSTCL was refractory to the chemotherapy and the patient died 7 months after the initial diagnosis because of haematemesis induced by Mallory-Weiss syndrome. Conclusion This is the first recorded case of coexistent HCL and HSTCL in the same patient. A multidisciplinary approach, encompassing careful morphology interpretation, immunophenotypic, cytogenetic and molecular analyses, is mandatory to obtain an accurate diagnosis of composite lymphoma. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9354870531161685. PMID:24621139

2014-01-01

52

Normal human Merkel cells are present in epidermal cell populations isolated and cultured from glabrous and hairy skin sites.  

PubMed

The Merkel cell is a highly specialized cell that primarily acts as a slowly adapting mechanoreceptor. Merkel cells are scarce in normal skin but can be identified by the expression of distinct keratin filaments. Merkel cells constitute a very unique population and many questions still remain as to their origin, number, proliferative capacity, and functions in cutaneous biology. The dissociation of epidermal cells from skin is a widely used technique to extract and culture keratinocytes. We took advantage of a two-step extraction method to quantify keratin-20-expressing Merkel cells among total cutaneous cells obtained from either hairy or glabrous skin biopsies. Flow cytometry analysis revealed that keratin-20-labeled Merkel cells represent between 3.6% and 5.7% of freshly dissociated basal epidermal cells. No significant differences were seen between samples derived from glabrous palmar and hairy anatomic sites, from children and adult, respectively. We also report on the presence of Merkel cells in primary and first subcultures of epidermal cells indicating their capacity to remain viable after extraction from skin of various anatomic sites. To our knowledge, this is the first demonstration of nontumorigenic human Merkel cells in culture in vitro. The persistence of a small number of Merkel cells in culture suggests that, with the development of appropriate culture conditions, these cells could be amplified and further studied to unravel long-standing questions relative to their paracrine function or epithelial origin. PMID:12542538

Fradette, Julie; Larouche, Danielle; Fugère, Claudia; Guignard, Rina; Beauparlant, Annie; Couture, Véronique; Caouette-Laberge, Louise; Roy, Alphonse; Germain, Lucie

2003-02-01

53

Leukemia cells induce changes in human bone marrow stromal cells  

PubMed Central

Background Bone marrow stromal cells (BMSCs) are multipotent cells that support angiogenesis, wound healing, and immunomodulation. In the hematopoietic niche, they nurture hematopoietic cells, leukemia, tumors and metastasis. BMSCs secrete of a wide range of cytokines, growth factors and matrix proteins which contribute to the pro-tumorigenic marrow microenvironment. The inflammatory cytokines IFN-? and TNF-? change the BMSC secretome and we hypothesized that factors produced by tumors or leukemia would also affect the BMSC secretome and investigated the interaction of leukemia cells with BMSCs. Methods BMSCs from healthy subjects were co-cultured with three myeloid leukemia cell lines (TF-1, TF-1? and K562) using a trans-well system. Following co-culture, the BMSCs and leukemia cells were analyzed by global gene expression analysis and culture supernatants were analyzed for protein expression. As a control, CD34+ cells were also cocultured with BMSCs. Results Co-culture induced leukemia cell gene expression changes in stem cell pluripotency, TGF-? signaling and carcinoma signaling pathways. BMSCs co-cultured with leukemia cells up-regulated a number of proinflammatory genes including IL-17 signaling-related genes and IL-8 and CCL2 levels were increased in co-culture supernatants. In contrast, purine metabolism, mTOR signaling and EIF2 signaling pathways genes were up-regulated in BMSCs co-cultured with CD34+ cells. Conclusions BMSCs react to the presence of leukemia cells undergoing changes in the cytokine and chemokine secretion profiles. Thus, BMSCs and leukemia cells both contribute to the creation of a competitive niche more favorable for leukemia stem cells. PMID:24304929

2013-01-01

54

Targeting leukemia stem cells: The new goal of therapy in adult acute myeloid leukemia  

PubMed Central

The most popular view of hematopoietic cell lineage organization is that of complex reactive or adaptative systems. Leukemia contains a subpopulation of cells that display characteristics of stem cells. These cells maintain tumor growth. The properties of leukemia stem cells indicate that current conventional chemotherapy, directed against the bulk of the tumor, will not be effective. Leukemia stem cells are quiescent and do not respond to cell cycle-specific cytotoxic agents used to treat leukemia and thus contribute to treatment failure. New strategies are required that specifically target this malignant stem cell population. PMID:21607107

Thomas, Xavier

2009-01-01

55

Adult T-cell leukemia/lymphoma  

PubMed Central

Adult T-cell leukemia/lymphoma is a rare malignancy associated with the human retrovirus human T-cell lymphotropic virus type 1. It is characterized by the proliferation of highly pleomorphic lymphocytes. Involvement of peripheral blood, bone marrow, lymph nodes, spleen, and extranodal sites such as skin, liver, gastrointestinal tract, and central nervous system can occur. There are four distinct clinical variants, and the prognosis and clinical course range from highly aggressive to a more protracted course depending on the subtype. We describe a man with de novo adult T-cell leukemia/lymphoma and discuss the unique clinical, morphologic, immunophenotypic, and molecular features of this entity. PMID:24982574

Burch, Micah; Krause, John R.

2014-01-01

56

Alisertib, Bortezomib, and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or B-cell Low Grade Non-Hodgkin Lymphoma  

ClinicalTrials.gov

Chronic Lymphocytic Leukemia; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

2014-11-21

57

Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth  

SciTech Connect

Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation, and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.

Wang, Jiying [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China)] [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China); Rao, Qing, E-mail: raoqing@gmail.com [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China)] [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China); Wang, Min; Wei, Hui; Xing, Haiyan; Liu, Hang; Wang, Yanzhong; Tang, Kejing; Peng, Leiwen; Tian, Zheng; Wang, Jianxiang [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China)] [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China)

2009-09-04

58

Obatoclax Mesylate, Vincristine Sulfate, Doxorubicin Hydrochloride, and Dexrazoxane Hydrochloride in Treating Young Patients With Relapsed or Refractory Solid Tumors, Lymphoma, or Leukemia  

ClinicalTrials.gov

Acute Leukemias of Ambiguous Lineage; Acute Undifferentiated Leukemia; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Small Intestine Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

2014-04-30

59

Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia  

ClinicalTrials.gov

B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

2014-05-22

60

Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation  

ClinicalTrials.gov

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

2013-07-03

61

Cell death sensitization of leukemia cells by opioid receptor activation  

PubMed Central

Cyclic AMP (cAMP) regulates a number of cellular processes and modulates cell death induction. cAMP levels are altered upon stimulation of specific G-protein-coupled receptors inhibiting or activating adenylyl cyclases. Opioid receptor stimulation can activate inhibitory Gi-proteins which in turn block adenylyl cyclase activity reducing cAMP. Opioids such as D,L-methadone induce cell death in leukemia cells. However, the mechanism how opioids trigger apoptosis and activate caspases in leukemia cells is not understood. In this study, we demonstrate that downregulation of cAMP induced by opioid receptor activation using the opioid D,L-methadone kills and sensitizes leukemia cells for doxorubicin treatment. Enhancing cAMP levels by blocking opioid-receptor signaling strongly reduced D,L-methadone-induced apoptosis, caspase activation and doxorubicin-sensitivity. Induction of cell death in leukemia cells by activation of opioid receptors using the opioid D,L-methadone depends on critical levels of opioid receptor expression on the cell surface. Doxorubicin increased opioid receptor expression in leukemia cells. In addition, the opioid D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux in leukemia cells, suggesting that the opioid D,L-methadone as well as doxorubicin mutually increase their cytotoxic potential. Furthermore, we found that opioid receptor activation using D,L-methadone alone or in addition to doxorubicin inhibits tumor growth significantly in vivo. These results demonstrate that opioid receptor activation via triggering the downregulation of cAMP induces apoptosis, activates caspases and sensitizes leukemia cells for doxorubicin treatment. Hence, opioid receptor activation seems to be a promising strategy to improve anticancer therapies. PMID:23633472

Friesen, Claudia; Roscher, Mareike; Hormann, Inis; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf A.; Debatin, Klaus-Michael; Miltner, Erich

2013-01-01

62

Human T-cell leukemia virus types I and II exhibit different DNase I protection patterns.  

PubMed Central

Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are human retroviruses which normally infect T-lymphoid cells. HTLV-I infection is associated with adult T-cell leukemia-lymphoma, and HTLV-II is associated with an indolent form of hairy-cell leukemia. To identify potential transcriptional regulatory elements of these two related human retroviruses, we performed DNase I footprinting of both the HTLV-I and HTLV-II long terminal repeats (LTRs) by using extracts prepared from uninfected T cells, HTLV-I and HTLV-II transformed T cells, and HeLa cells. Five regions of the HTLV-I LTR and three regions of the HTLV-II LTR showed protection by DNase I footprinting. All three of the 21-base-pair repeats previously shown to be important in HTLV transcriptional regulation were protected in the HTLV-I LTR, whereas only one of these repeats was protected in the HTLV-II LTR. Several regions exhibited altered protection in extracts prepared from lymphoid cells as compared with HeLa cells, but there were minimal differences in the protection patterns between HTLV-infected and uninfected lymphoid extracts. A number of HTLV-I and HTLV-II LTR fragments which contained regions showing protection in DNase I footprinting were able to function as inducible enhancer elements in transient CAT gene expression assays in the presence of the HTLV-II tat protein. The alterations in the pattern of the cellular proteins which bind to the HTLV-I and HTLV-II LTRs may in part be responsible for differences in the transcriptional regulation of these two related viruses. Images PMID:2831395

Altman, R; Harrich, D; Garcia, J A; Gaynor, R B

1988-01-01

63

Molecular Hallmarks of Adult T Cell Leukemia  

PubMed Central

The molecular hallmarks of adult T cell leukemia (ATL) comprise outstanding deregulations of signaling pathways that control the cell cycle, resistance to apoptosis, and proliferation of leukemic cells, all of which have been identified by early excellent studies. Nevertheless, we are now confronted the therapeutic difficulties of ATL that is a most aggressive T cell leukemia/lymphoma. Using next-generation strategies, emerging molecular characteristics such as specific surface markers and an additional catalog of signals affecting the fate of leukemic cells have been added to the molecular hallmarks that constitute an organizing principle for rationalizing the complexities of ATL. Although human T cell leukemia virus type 1 is undoubtedly involved in ATL leukemogenesis, most leukemic cells do not express the viral protein Tax. Instead, cellular gene expression changes dominate homeostasis disorders of infected cells and characteristics of ATL. In this review, we summarize the state of the art of ATL molecular pathology, which supports the biological properties of leukemic cells. In addition, we discuss the recent discovery of two molecular hallmarks of potential generality; an abnormal microRNA pattern and epigenetic reprogramming, which strongly involve the imbalance of the molecular network of lymphocytes. Global analyses of ATL have revealed the functional impact of crosstalk between multifunctional pathways. Clinical and biological studies on signaling inhibitory agents have also revealed novel oncogenic drivers that can be targeted in future. ATL cells, by deregulation of such pathways and their interconnections, may become masters of their own destinies. Recognizing and understanding of the widespread molecular applicability of these concepts will increasingly affect the development of novel strategies for treating ATL. PMID:23060864

Yamagishi, Makoto; Watanabe, Toshiki

2012-01-01

64

Monoclonal antibody targets, kills leukemia cells  

Cancer.gov

Researchers at the University of California, San Diego Moores Cancer Center have identified a humanized monoclonal antibody that targets and directly kills chronic lymphocytic leukemia (CLL) cells. The findings, published in the online Early Edition of the Proceedings of the National Academy of Sciences on March 25, 2013 represent a potential new therapy for treating at least some patients with CLL, the most common type of blood cancer in the United States.

65

NOTCH1-induced T-cell leukemia in transgenic zebrafish  

Microsoft Academic Search

Activating mutations in the NOTCH1 gene have been found in about 60% of patients with T-cell acute lymphoblastic leukemia (T-ALL). In order to study the molecular mechanisms by which altered Notch signaling induces leukemia, a zebrafish model of human NOTCH1-induced T-cell leukemia was generated. Seven of sixteen mosaic fish developed a T-cell lymphoproliferative disease at about 5 months. These neoplastic

J Chen; C Jette; J P Kanki; J C Aster; A T Look; J D Griffin

2007-01-01

66

Human Adult T-Cell Leukemia Virus: Complete Nucleotide Sequence of the Provirus Genome Integrated in Leukemia Cell DNA  

Microsoft Academic Search

Human retrovirus adult T-cell leukemia virus (ATLV) has been shown to be closely associated with human adult T-cell leukemia (ATL) [Yoshida, M., Miyoshi, I. & Hinuma, Y. (1982) Proc. Natl. Acad. Sci. USA 79, 2031-2035]. The provirus of ATLV integrated in DNA of leukemia T cells from a patient with ATL was molecularly cloned and the complete nucleotide sequence of

Motoharu Seiki; Seisuke Hattori; Yoko Hirayama; Mitsuaki Yoshida

1983-01-01

67

Cell cycle control in acute myeloid leukemia  

PubMed Central

Acute myeloid leukemia (AML) is the result of a multistep transforming process of hematopoietic precursor cells (HPCs) which enables them to proceed through limitless numbers of cell cycles and to become resistant to cell death. Increased proliferation renders these cells vulnerable to acquiring mutations and may favor leukemic transformation. Here, we review how deregulated cell cycle control contributes to increased proliferation in AML and favors genomic instability, a prerequisite to confer selective advantages to particular clones in order to adapt and independently proliferate in the presence of a changing microenvironment. We discuss the connection between differentiation and proliferation with regard to leukemogenesis and outline the impact of specific alterations on response to therapy. Finally, we present examples, how a better understanding of cell cycle regulation and deregulation has already led to new promising therapeutic strategies. PMID:22957304

Schnerch, Dominik; Yalcintepe, Jasmin; Schmidts, Andrea; Becker, Heiko; Follo, Marie; Engelhardt, Monika; Wäsch, Ralph

2012-01-01

68

Acute myelogenous leukemia stem cells: From Bench to Bedside  

PubMed Central

Despite reaching remission with traditional chemotherapy, most adult patients with acute myeloid leukemia (AML) will relapse and die of their disease. Numerous studies have identified a rare subset of leukemia cells that evade traditional chemotherapy and are capable of self-renewal and initiating leukemia. These cells are thought to be responsible for relapse and are termed leukemia stem cells (LSCs). This article will review the current LSC translational research and focus on new approaches to detect LSC burden and its prognostic implications, as well as the identification and development of therapeutic agents active against LSCs. PMID:22713929

Rico, J. Felipe; Hassane, Duane C.; Guzman, Monica L.

2015-01-01

69

Laser activated nanothermolysis of leukemia cells monitored by photothermal microscopy  

NASA Astrophysics Data System (ADS)

We are developing new diagnostic and therapeutic technologies for leukemia based on selective targeting of leukemia cells with gold nanoparticles and thermomechanical destruction of the tumor cells with laser-induced microbubbles. Clusters of spherical gold nanoparticles that have strong optical absorption of laser pulses at 532 nm served as nucleation sites of vapor microbubbles. The nanoparticles were targeted selectively to leukemia cells using leukemia-specific surface receptors and a set of two monoclonal antibodies. Application of a primary myeloid-specific antibody to tumor cells followed by targeting the cells with 30-nm nanoparticles conjugated with a secondary antibody (IgG) resulted in formation of nanoparticulate clusters due to aggregation of IgGs. Formation of clusters resulted in substantial decrease of the damage threshold for target cells. The results encourage development of Laser Activated Nanothermolysis as a Cell Elimination Therapy (LANCET) for leukemia. The proposed technology can be applied separately or in combination with chemotherapy for killing leukemia cells without damage to other blood cells. Potential applications include initial reduction of concentration of leukemia cells in blood prior to chemotherapy and treatment of residual tumor cells after the chemotherapy. Laser-induced bubbles in individual cells and cell damage were monitored by analyzing profile of photothermal response signals over the entire cell after irradiation with a single 10-ns long laser pulse. Photothermal microscopy was utilized for imaging formation of microbubbles around nanoparticulate clusters.

Lapotko, Dmitri; Lukianova, Ekaterina; Shnip, Alexander; Zheltov, George; Potapnev, Michail; Savitsky, Valeriy; Klimovich, Olga; Oraevsky, Alexander

2005-04-01

70

INITIATION AND PROLIFERATION OF GOSSYPOL-PRODUCING COTTON HAIRY ROOTS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Hairy roots are masses of differentiated, transformed cells resulting from infection with Rhizobium rhizogenes (ATCC 15834) (Agrobacterium rhizogenes). Hairy root cultures derived from many plant species have been valuable research tools for producing secondary plant metabolites and for examining ne...

71

Adult T-cell leukemia-lymphoma.  

PubMed

Adult T-cell leukemia-lymphoma (ATL) was first described in 1977 as a distinct clinico-pathological entity with a suspected viral etiology. Subsequently, a novel RNA retrovirus, human T-cell leukemia/lymphotropic virus type 1 (HTLV-1) was isolated from a cell line established from the leukemic cells of an ATL patient, and the finding of a clear association with ATL led to its inclusion among human carcinogenic pathogens. The three major routes of HTLV-1 transmission are mother-to-child infections via breast milk, sexual intercourse, and blood transfusions. HTLV-1 infection early in life, presumably from breast feeding, is crucial in the development of ATL. The diversity in clinical features and prognosis of patients with this disease has led to its subtype-classification into four categories, acute, lymphoma, chronic, and smoldering types defined by organ involvement, and LDH and calcium values. In cases of acute, lymphoma, or unfavorable chronic subtypes (aggressive ATL), intensive chemotherapy such as VCAP-AMP-VECP is usually recommended. In cases of favorable chronic or smoldering ATL (indolent ATL), watchful waiting until disease progression has been recommended although the long term prognosis was inferior to those of, for instance, chronic lymphoid leukemia. Retrospective analysis suggested that the combination of interferon alpha and zidovudine was apparently promising for the treatment of ATL, especially for types with leukemic manifestation. Allogeneic hematopoietic stem cell transplantation is also promising for the treatment of aggressive ATL possibly reflecting graft vs. ATL effect. Several new agent-trials for ATL are ongoing and in preparation, including a defucosylated humanized anti-CC chemokine receptor 4 monoclonal antibody. Two steps should be considered for the prevention of HTLV-1-associated ATL. The first is the prevention of HTLV-1 infections and the second is the prevention of ATL among HTLV-1 carriers. So far, no agent has been found to be effective for the latter. Further investigation on the pathogenesis of ATL is crucial for the prevention and treatment of this refractory leukemia-lymphoma. PMID:22507774

Tsukasaki, Kunihiro

2012-04-01

72

Monoclonal Integration of Human T-Cell Leukemia Provirus in All Primary Tumors of Adult T-Cell Leukemia Suggests Causative Role of Human T-Cell Leukemia Virus in the Disease  

Microsoft Academic Search

The genome of human T-cell leukemia virus (HTLV) was surveyed in fresh tumor cells of 163 patients with lymphoma and leukemia from the southwest part of Japan where adult T-cell leukemia (ATL) is endemic. Leukemic cells of all 88 cases of ATL tested so far were found to contain the provirus genome and also found to be monoclonal with respect

M. Yoshida; M. Seiki; K. Yamaguchi; K. Takatsuki

1984-01-01

73

Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma  

ClinicalTrials.gov

B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

2013-07-01

74

Gossypol-Induced Differentiation in Human Leukemia HL-60 Cells.  

PubMed

The main treatment of leukemia is traditional radiochemotherapy, which is associated with serious side effects. In the past twenty years, differentiation was found as an important effective measure to treat leukemia with fewer side effects. Gossypol, a natural compound which has been used as an effective contraceptive drug, has been proposed to be a potent drug to treat leukemia, but the differentiation effect has not been studied. In the present study, we investigated the pro-differentiated effects, in vitro, of gossypol on the classic human myeloid leukemia HL-60 cell line. The effects of gossypol were investigated by using morphological changes, nitroblue tetrazolium (NBT) reduction, surface markers, cell-cycle analysis and Western blot analysis, etc. When HL-60 cells were incubated with low concentrations of gossypol (2-5?M) for 48hr, a prominent G0/G1 arrest was observed. At 96 hr of treatment, 90% of HL-60 cells differentiated, as evidenced by morphological changes, NBT reduction, and increase in cell surface expression of some molecules were detected. This study is the first to identify gossypol's pro-differentiated effects on the leukemia cell line, and it induced differentiation through the PBK (PDZ-binding kinase)/TOPK (T-LAKcell-originated protein kinase) (PBK/TOPK) pathway. It is concluded that gossypol could induce differentiation in the leukemia HL-60 cells, and it may be a potential therapeutic agent, chemoprevention or chemotherapeutic adjuvant especially in combination drug therapy for leukemia. PMID:23675007

Wang, Wen-Qing; Li, Rong; Bai, Qing-Xian; Liu, Yu-Hong; Zhang, Wei-Ping; Wang, Juan-Hong; Wang, Zhe; Li, Yuan-Fei; Chen, Xie-Qun; Huang, Gao-Sheng

2006-12-01

75

Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I.  

PubMed Central

The human T-cell leukemia virus type I Tax protein trans-activates several cellular genes implicated in T-cell replication and activation. To investigate its leukemogenic potential, Tax was targeted to the mature T-lymphocyte compartment in transgenic mice by using the human granzyme B promoter. These mice developed large granular lymphocytic leukemia, demonstrating that expression of Tax in the lymphocyte compartment is sufficient for the development of leukemia. Furthermore, these observations suggest that human T-cell leukemia virus infection may be involved in the development of large granular lymphocytic leukemia. Images Fig. 1 Fig. 2 Fig. 4 PMID:7862633

Grossman, W J; Kimata, J T; Wong, F H; Zutter, M; Ley, T J; Ratner, L

1995-01-01

76

Expression of a leukemia-associated antigen (CAMAL) in four myeloid leukemia cell lines.  

PubMed

We have previously described the detection and partial characterization of a common myelogenous leukemia-associated antigen (CAMAL), in CGL and ANLL patients. Both polyclonal and monoclonal (CAMAL-1) antibodies have been raised to p70 (CAMAL) and have been shown to react with both p70 and myeloid leukemia cell preparations. p70 (CAMAL) has been shown to be a monomeric protein of Mr 70,000 and pI 7.2 and was also detectable in the myeloid leukemia cell lines HL60, KG1, K562 and U937, but not in the lymphocytic cell lines Molt-4, Hut-78 and CEM by immunoprecipitation from iodinated cell samples. Using [35S] methionine-labeled cell lines and immunoprecipitation, we have demonstrated the constitutive expression of p70 as well as a major component at p58 and a number at lower molecular weights in the myeloid leukemia cell lines HL60, KG1, K562 and U937, but not in the lymphocytic leukemia cell lines Molt-4, Hut-78 and CEM. The implications of these observations are discussed. PMID:3172816

Shipman, R C; Levy, J G

1988-01-01

77

Dendritic Cell-Based Immunotherapy for Myeloid Leukemias  

PubMed Central

Acute and chronic myeloid leukemia (AML, CML) are hematologic malignancies arising from oncogene-transformed hematopoietic stem/progenitor cells known as leukemia stem cells (LSCs). LSCs are selectively resistant to various forms of therapy including irradiation or cytotoxic drugs. The introduction of tyrosine kinase inhibitors has dramatically improved disease outcome in patients with CML. For AML, however, prognosis is still quite dismal. Standard treatments have been established more than 20?years ago with only limited advances ever since. Durable remission is achieved in less than 30% of patients. Minimal residual disease (MRD), reflected by the persistence of LSCs below the detection limit by conventional methods, causes a high rate of disease relapses. Therefore, the ultimate goal in the treatment of myeloid leukemia must be the eradication of LSCs. Active immunotherapy, aiming at the generation of leukemia-specific cytotoxic T cells (CTLs), may represent a powerful approach to target LSCs in the MRD situation. To fully activate CTLs, leukemia antigens have to be successfully captured, processed, and presented by mature dendritic cells (DCs). Myeloid progenitors are a prominent source of DCs under homeostatic conditions, and it is now well established that LSCs and leukemic blasts can give rise to “malignant” DCs. These leukemia-derived DCs can express leukemia antigens and may either induce anti-leukemic T cell responses or favor tolerance to the leukemia, depending on co-stimulatory or -inhibitory molecules and cytokines. This review will concentrate on the role of DCs in myeloid leukemia immunotherapy with a special focus on their generation, application, and function and how they could be improved in order to generate highly effective and specific anti-leukemic CTL responses. In addition, we discuss how DC-based immunotherapy may be successfully integrated into current treatment strategies to promote remission and potentially cure myeloid leukemias. PMID:24427158

Schürch, Christian M.; Riether, Carsten; Ochsenbein, Adrian F.

2013-01-01

78

Dendritic cell-based immunotherapy for myeloid leukemias.  

PubMed

Acute and chronic myeloid leukemia (AML, CML) are hematologic malignancies arising from oncogene-transformed hematopoietic stem/progenitor cells known as leukemia stem cells (LSCs). LSCs are selectively resistant to various forms of therapy including irradiation or cytotoxic drugs. The introduction of tyrosine kinase inhibitors has dramatically improved disease outcome in patients with CML. For AML, however, prognosis is still quite dismal. Standard treatments have been established more than 20?years ago with only limited advances ever since. Durable remission is achieved in less than 30% of patients. Minimal residual disease (MRD), reflected by the persistence of LSCs below the detection limit by conventional methods, causes a high rate of disease relapses. Therefore, the ultimate goal in the treatment of myeloid leukemia must be the eradication of LSCs. Active immunotherapy, aiming at the generation of leukemia-specific cytotoxic T cells (CTLs), may represent a powerful approach to target LSCs in the MRD situation. To fully activate CTLs, leukemia antigens have to be successfully captured, processed, and presented by mature dendritic cells (DCs). Myeloid progenitors are a prominent source of DCs under homeostatic conditions, and it is now well established that LSCs and leukemic blasts can give rise to "malignant" DCs. These leukemia-derived DCs can express leukemia antigens and may either induce anti-leukemic T cell responses or favor tolerance to the leukemia, depending on co-stimulatory or -inhibitory molecules and cytokines. This review will concentrate on the role of DCs in myeloid leukemia immunotherapy with a special focus on their generation, application, and function and how they could be improved in order to generate highly effective and specific anti-leukemic CTL responses. In addition, we discuss how DC-based immunotherapy may be successfully integrated into current treatment strategies to promote remission and potentially cure myeloid leukemias. PMID:24427158

Schürch, Christian M; Riether, Carsten; Ochsenbein, Adrian F

2013-01-01

79

Gene expression profiling in T-cell acute lymphoblastic leukemia  

Microsoft Academic Search

T-cell acute lymphoblastic leukemia (T-ALL) presents a difficult medical problem. T-ALL’s clinical features and the biological properties of the leukemia cells are not predictive of prognosis, and thus have not been useful for risk-specific adjustments in therapeutic intensity. Microarray gene expression analyses of T-cell leukemic lymphoblasts have not only improved our understanding of the biological heterogeneity of this disease but

Adolfo A Ferrando; A. Thomas Look

2003-01-01

80

Targeting Myelogenous Leukemia Stem Cells: Role of the Circulation  

PubMed Central

Unlike stem cells from solid tumors, the stem cells which initiate myelogenous leukemias arise in marrow, an organ with a unique circulation which allows ready access of leukemia cells, including leukemia stem cells (LSCs), to the vasculature. This poses unique problems in the targeting of LSCs since these cells are found circulating in the majority of leukemia cases at diagnosis and are usually not detectable during remission states. Because most cases of leukemia relapse, it is suggested that LSCs remain quiescent in the marrow until they eventually proliferate and circulate again. This indicates that effective targeting of LSCs must occur not only in peripheral circulation but in the micro-circulation of the marrow. Targeting such interactions may overcome cell adhesion-mediated treatment resistance, other multi-drug resistance mechanisms, and opportunities for clonal evolution in the marrow environment. Targeting selectins and integrins, signal transduction mediators, and chemokine/cytokine networks in the marrow micro-circulation may aid in abrogating leukemia-initiating stem cells which contribute to disease relapse. LSCs possess surface antigen profiles and signal transduction activation profiles which may allow differential targeting as compared with normal hematopoietic stem cells. PMID:22876360

Liesveld, Jane

2012-01-01

81

ARTICLES Defective DNA Repair in Cells With Human T-Cell Leukemia\\/Bovine Leukemia Viruses: Role of tax Gene  

Microsoft Academic Search

Background: Human T-cell leukemia virus (HTLV)\\/bovine leukemia virus (BLV) group retroviruses, which cause he- matopoietic cancers, encode a unique protein, Tax, involved in the transformation of infected cells. Our purpose was to determine whether the mechanism by which Tax protein induces transformation in HTLV- or BLV-infected cells in- volves DNA damage. Methods: We used a micronucleus as- say to measure

Sean M. Philpott; Gertrude C. Buehring

1999-01-01

82

In vivo eradication of MLL/ENL leukemia cells by NK cells in the absence of adaptive immunity.  

PubMed

It remains unclear how the immune system affects leukemia development. To clarify the significance of the presence of immune systems in leukemia development, we transferred MLL/ENL leukemia cells into immune-competent or immune-deficient mice without any preconditioning including irradiation. The wild-type mice did not develop leukemia, whereas all the Rag2(-/-)?c(-/-) mice lacking both adaptive immune cells and natural killer (NK) cells developed leukemia, indicating that leukemia cells were immunologically rejected. Interestingly, leukemia cells were also rejected in 60% of the Rag2(-/-) mice that lacked adaptive immune cells but possessed NK cells, suggesting that NK cells play a substantial role in the rejection of leukemia. Moreover, engraftment of leukemia cells was enhanced by NK cell depletion in Rag2(-/-) recipients and inhibited by transfer of NK cells into Rag2(-/-)?c(-/-) recipients. Upregulation of NKG2D (NK group 2, member D) ligands in MLL/ENL leukemia cells caused elimination of leukemia cells by NK cells. Finally, we found that leukemia cells resistant to elimination by NK cells had been selected during leukemia development in Rag2(-/-) recipients. These results demonstrate that NK cells can eradicate MLL/ENL leukemia cells in vivo in the absence of adaptive immunity, thus suggesting that NK cells can play a potent role in immunosurveillance against leukemia. PMID:24336127

Nakata, J; Nakano, K; Okumura, A; Mizutani, Y; Kinoshita, H; Iwai, M; Hasegawa, K; Morimoto, S; Fujiki, F; Tatsumi, N; Nakajima, H; Nakae, Y; Nishida, S; Tsuboi, A; Oji, Y; Oka, Y; Sugiyama, H; Kumanogoh, A; Hosen, N

2014-06-01

83

Expression profile of CREB knockdown in myeloid leukemia cells  

Microsoft Academic Search

BACKGROUND: The cAMP Response Element Binding Protein, CREB, is a transcription factor that regulates cell proliferation, differentiation, and survival in several model systems, including neuronal and hematopoietic cells. We demonstrated that CREB is overexpressed in acute myeloid and leukemia cells compared to normal hematopoietic stem cells. CREB knockdown inhibits leukemic cell proliferation in vitro and in vivo, but does not

Matteo Pellegrini; Jerry C Cheng; Jon Voutila; Dejah Judelson; Julie Taylor; Stanley F Nelson; Kathleen M Sakamoto

2008-01-01

84

The role of natural killer cells in chronic myeloid leukemia  

PubMed Central

Chronic myeloid leukemia is a neoplasia resulting from a translocation between chromosomes 9 and 22 producing the BCR-ABL hybrid known as the Philadelphia chromosome (Ph). In chronic myeloid leukemia a proliferation of malignant myeloid cells occurs in the bone marrow due to excessive tyrosine kinase activity. In order to maintain homeostasis, natural killer cells, by means of receptors, identify the major histocompatibility complex on the surface of tumor cells and subsequently induce apoptosis. The NKG2D receptor in the natural killer cells recognizes the transmembrane proteins related to major histocompatibility complex class I chain-related genes A and B (MICA and MICB), and it is by the interaction between NKG2D and MICA that natural killer cells exert cytotoxic activity against chronic myeloid leukemia tumor cells. However, in the case of chronic exposure of the NKG2D receptor, the MICA ligand releases soluble proteins called sMICA from the tumor cell surface, which negatively modulate NKG2D and enable the tumor cells to avoid lysis mediated by the natural killer cells. Blocking the formation of sMICA may be an important antitumor strategy. Treatment using tyrosine kinase inhibitors induces modulation of NKG2DL expression, which could favor the activity of the natural killer cells. However this mechanism has not been fully described in chronic myeloid leukemia. In the present study, we analyze the role of natural killer cells to reduce proliferation and in the cellular death of tumor cells in chronic myeloid leukemia. PMID:23049299

Danier, Anna Carolyna Araújo; de Melo, Ricardo Pereira; Napimoga, Marcelo Henrique; Laguna-Abreu, Maria Theresa Cerávolo

2011-01-01

85

Laser nanothermolysis of human leukemia cells using functionalized plasmonic nanoparticles  

PubMed Central

In the present work, we present the use of gold nanorods as plasmonic nanoparticles for selective photothermal therapy of human acute (HL-60) and chronicle (K-562) leukemia cells using a near-infrared laser. We improved a published methodology of gold nanorods conjugation to generate high yields of narrow band gold nanorods with an optical absorption centered at 760 nm. The manufactured nanorods were pegylated and conjugated with monoclonal antibody to become non-toxic as biocompatible nanothermolysis agent. Gold nanorods are synthesized and conjugated to CD33 monoclonal antibody. After pegylation, or conjugation with CD33 antibody, gold nanorods were non-toxic to acute and chronic leukemia cells. Our modified gold nanorods CD33 conjugates shown high level of accumulation for both leukemia cell lines, and successful used for nanothermolysis of human leukemia cells in vitro. Each sample was illuminated with 1 or 3 laser shots as for low and for high laser fluence. The radiation was provided by a Quanta Systems q-switched titanium sapphire laser, and the system was designed for maximum sample coverage using non-focused illumination. HL-60 and K-562 cells were treated for 45 min with gold nanorods CD33 conjugated, or with pegylated gold nanorods. The effect of pulsed-laser nanothermolysis for acute and chronic leukemia cells were investigated with cell counting for number of living cells, percentage of cell death and functional parameters such as damage of cell membrane and metabolic activity. Gold nanorods CD33 conjugates significantly increase cell damage for low fluence laser and completely destroyed cancer cells after 3 pulses for low fluence (acute leukemia) and for high fluence laser as for HL-60 (acute) and for K-562 (chronicle) leukemia cells. PMID:22720194

Liopo, Anton V.; Conjusteau, André; Konopleva, Marina; Andreeff, Michael; Oraevsky, Alexander A.

2012-01-01

86

Laser nanothermolysis of human leukemia cells using functionalized plasmonic nanoparticles.  

PubMed

In the present work, we present the use of gold nanorods as plasmonic nanoparticles for selective photothermal therapy of human acute (HL-60) and chronicle (K-562) leukemia cells using a near-infrared laser. We improved a published methodology of gold nanorods conjugation to generate high yields of narrow band gold nanorods with an optical absorption centered at 760 nm. The manufactured nanorods were pegylated and conjugated with monoclonal antibody to become non-toxic as biocompatible nanothermolysis agent. Gold nanorods are synthesized and conjugated to CD33 monoclonal antibody. After pegylation, or conjugation with CD33 antibody, gold nanorods were non-toxic to acute and chronic leukemia cells. Our modified gold nanorods CD33 conjugates shown high level of accumulation for both leukemia cell lines, and successful used for nanothermolysis of human leukemia cells in vitro. Each sample was illuminated with 1 or 3 laser shots as for low and for high laser fluence. The radiation was provided by a Quanta Systems q-switched titanium sapphire laser, and the system was designed for maximum sample coverage using non-focused illumination. HL-60 and K-562 cells were treated for 45 min with gold nanorods CD33 conjugated, or with pegylated gold nanorods. The effect of pulsed-laser nanothermolysis for acute and chronic leukemia cells were investigated with cell counting for number of living cells, percentage of cell death and functional parameters such as damage of cell membrane and metabolic activity. Gold nanorods CD33 conjugates significantly increase cell damage for low fluence laser and completely destroyed cancer cells after 3 pulses for low fluence (acute leukemia) and for high fluence laser as for HL-60 (acute) and for K-562 (chronicle) leukemia cells. PMID:22720194

Liopo, Anton V; Conjusteau, André; Konopleva, Marina; Andreeff, Michael; Oraevsky, Alexander A

2012-01-01

87

T-cell acute lymphoid leukemia resembling Burkitt leukemia cell morphology: A case report  

PubMed Central

Biphenotypic acute leukemia (BAL) is an uncommon type of cancer, which accounts for <5% of all adult ALs. Based upon a previously described scoring system, the European Group for the Immunological Classification of Leukemias (EGIL) proposed a set of diagnostic criteria for BAL. This scoring system is based upon the number and degree of specificity of several markers for myeloid or T/B-lymphoid blasts. The present study describes a case of T-cell acute lymphoblastic leukemia (T-ALL) with Burkitt-like cytology, which according to the French-American-British classification, corresponded to a diagnosis of Burkitt type L3 ALL. Flow cytometry analysis demonstrated that the blasts were positive for T-lymphoid markers, cytoplasmic cluster of differentiation (CD)3, CD7 and CD56, and myeloid markers, CD13, CD33 and CD15. At first, a diagnosis of BAL was suggested by the EGIL score, however, according to the 2008 World Health Organization criteria, a case of T-ALL with aberrant myeloid markers was established. The study also reviewed the literature and discussed the limitations of the EGIL scoring system in clinical decision making, to aid in the selection of an appropriate therapeutic regimen. PMID:25663889

YUE, QINGFANG; LIU, XINYUE; CHEN, LEI; LIU, ZHONGPING; CHEN, WANXIN

2015-01-01

88

Recommendations of the SFH (French Society of Haematology) for the diagnosis, treatment and follow-up of hairy cell leukaemia.  

PubMed

Hairy cell leukaemia (HCL) is a rare haematological malignancy, with approximately 175 new incident cases in France. Diagnosis is based on a careful examination of the blood smear and immunophenotyping of the tumour cells, with a panel of four markers being used specifically to screen for hairy cells (CD11c, CD25, CD103 and CD123). In 2011, the V600E mutation of the BRAF gene in exon 15 was identified in HCL; being present in HCL, it is absent in the variant form of HCL (HCL-v) and in splenic red pulp lymphoma (SRPL), two entities related to HCL. The management of patients with HCL has changed in recent years. A poorer response to purine nucleoside analogues (PNAs) is observed in patients with more marked leukocytosis, bulky splenomegaly, an unmutated immunoglobulin variable heavy chain (IgVH) gene profile, use of VH4-34 or with TP53 mutations. We present the recommendations of a group of 11 experts belonging to a number of French hospitals. This group met in November 2013 to examine the criteria for managing patients with HCL. The ideas and proposals of the group are based on a critical analysis of the recommendations already published in the literature and on an analysis of the practices of clinical haematology departments with experience in managing these patients. The first-line treatment uses purine analogues: cladribine or pentostatin. The role of BRAF inhibitors, whether or not combined with MEK inhibitors, is discussed. The panel of French experts proposed recommendations to manage patients with HCL, which can be used in a daily practice. PMID:24994538

Cornet, Edouard; Delmer, Alain; Feugier, Pierre; Garnache-Ottou, Francine; Ghez, David; Leblond, Véronique; Levy, Vincent; Maloisel, Frédéric; Re, Daniel; Zini, Jean-Marc; Troussard, Xavier

2014-12-01

89

Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma  

ClinicalTrials.gov

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

2014-10-30

90

Signaling proteins and pathways affected by flavonoids in leukemia cells.  

PubMed

Flavonoids are a class of plant secondary metabolites that are found ubiquitously in plants and in the human diet. Our objective is to investigate the antiproliferative effects of flavonoids (baicalein, luteolin, genistein, apigenin, scutellarin, galangin, chrysin, and naringenin) toward leukemia cells (HL-60, NB4, U937, K562, Jurkat) as well as the relationship between their antileukemic potencies and molecular structures. At the proteomic level, we evaluate the effects of different flavonoids on the expression levels of various proteins using Protein Pathway Array (PPA) technology. Our results showed a dose-dependent cytotoxicity of flavonoids toward various types of leukemia cells. The results of PPA illustrated that flavonoids, such as baicalein, genistein, and scutellarin affected different proteins in different leukemia cell lines. Cell cycle regulatory proteins, such as CDK4, CDK6, Cyclin D1, Cyclin B1, p-CDC2, and p-RB were affected in different leukemia cells. Furthermore, we found that baicalein suppresses CDK4 and activates p-ERK in most leukemia cells; genistein mainly affects CDK4, p-ERK, p-CDC2, while scutellarin dysregulated the proteins, cell division control protein 42, Notch4, and XIAP. Collectively, a wide variety of dysregulation of key signaling proteins related to apoptosis and cell-cycle regulation contributes to the antileukemic properties of these flavonoids. PMID:25588108

Liu, Xiaoliang; Ye, Fei; Wu, Josephine; How, Brian; Li, Wei; Zhang, David Y

2015-01-01

91

Alvocidib, Fludarabine Phosphate, and Rituximab in Treating Patients With Lymphoproliferative Disorders or Mantle Cell Lymphoma  

ClinicalTrials.gov

B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Splenic Marginal Zone Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Untreated Hairy Cell Leukemia; Waldenström Macroglobulinemia

2013-06-03

92

Mitochondrial DNA sequence variation in single cells from leukemia patients  

PubMed Central

A high frequency of mtDNA somatic mutation has been observed in many tumors as well as in aging tissues. In this study, we analyzed the mtDNA control region sequence variation in 3534 single normal cells and individual blasts from 18 patients with leukemia and 10 healthy donors, to address the mutation process in leukemic cells. We found significant differences in mtDNA sequence, as represented by the number of haplotypes and the mean number of cells with each nonaggregate haplotype in a population of cells, in patients compared to controls. Patients with similar clinical leukemia types, particularly acute myeloid leukemia (AML), did not show a uniform pattern of sequence variation in single blasts. Some patients at relapse presented a complex shift of major haplotypes in single cells. Four patients showed high frequencies of cells containing mutations 189, 260, 16150, and 16488, respectively, as a result of clonal expansion and could be considered as potential markers for their respective disease progression. To our knowledge, this is the first large-scale study of mtDNA variation in single malignant cells. Our results suggest that the somatic mutation process in leukemia is complex, leading to diverse levels of genetic alterations due to either intrinsic aspects of leukemia pathophysiology or chemotherapy effects. PMID:16946307

Yao, Yong-Gang; Ogasawara, Yoji; Kajigaya, Sachiko; Molldrem, Jeffrey J.; Falcão, Roberto P.; Pintão, Maria-Carolina; McCoy, J. Philip; Rizzatti, Edgar Gil; Young, Neal S.

2007-01-01

93

75 FR 14391 - Diseases Associated With Exposure to Certain Herbicide Agents (Hairy Cell Leukemia and Other...  

Federal Register 2010, 2011, 2012, 2013, 2014

...committee report, Veterans and Agent Orange: Update 2008 (Update 2008). This proposed...SUPPLEMENTARY INFORMATION: Section 3 of the Agent Orange Act of 1991, Public Law 102-4, 105...States Code, as enacted by the Agent Orange Act of 1991, Public Law 102-4,...

2010-03-25

94

75 FR 53202 - Diseases Associated With Exposure to Certain Herbicide Agents (Hairy Cell Leukemia and Other...  

Federal Register 2010, 2011, 2012, 2013, 2014

...committee report, Veterans and Agent Orange: Update 2008 (Update 2008). This amendment...National Academies, Veterans and Agent Orange: Update 2008, The National Academies...National Academies, Veterans and Agent Orange: Update 2008, The National...

2010-08-31

95

Novel and Emerging Drugs for Acute Myeloid Leukemia  

PubMed Central

Acute myeloid leukemia (AML) is a challenging disease to treat with the majority of patients dying from their illness. While overall survival has been markedly prolonged in acute promyelocytic leukemia (APL), survival in younger adults with other subtypes of AML has only modestly improved over the last twenty years. Physicians who treat AML eagerly await drugs like Imatinib for chronic myeloid leukemia, Cladribine for hairy cell leukemia, and Rituximab for non-Hodgkin Lymphoma which have had an important impact on improving outcome. Recent research efforts have focused on refining traditional chemotherapeutic agents to make them more active in AML, targeting specific genetic mutations in myeloid leukemia cells, and utilizing novel agents such as Lenalidomide that have shown activity in other hematologic malignancies. Here, we focus on reviewing the recent literature on agents that may assume a role in clinical practice for patients with AML over the next five years. PMID:22483153

Stein, E.M.; Tallman, M.S.

2014-01-01

96

Adult T-cell leukemia/lymphoma not associated with human T-cell leukemia virus type I.  

PubMed Central

We describe five patients with adult T-cell leukemia/lymphoma (ATL) with neither integration of human T-cell leukemia virus type I (HTLV-I) into their leukemia cells nor anti-HTLV-I antibody in their sera. These findings indicate that HTLV-I may not have been involved in leukemogenesis in these patients. The clinicohematological, cytopathological, and immunological features of HTLV-I-negative ATL were exactly the same as those of HTLV-I-associated ATL. Leukemia cells with pleomorphic nuclei, generalized lymphadenopathy, hepatosplenomegaly, skin lesions, hypercalcemia, and elevated lactate dehydrogenase levels, all of which are characteristic features of typical ATL, were also seen in these patients with HTLV-I-negative ATL. Leukemia cells expressed T3, T4, and pan-T-cell antigens in three cases, and T3 and pan-T-cell antigens in two. All five patients had lived in ATL-nonendemic areas. The finding of HTLV-I-negative ATL suggests that factor(s) other than HTLV-I infection may be involved in ATL leukemogenesis. Images PMID:3012571

Shimoyama, M; Kagami, Y; Shimotohno, K; Miwa, M; Minato, K; Tobinai, K; Suemasu, K; Sugimura, T

1986-01-01

97

Leukomogenic factors downregulate heparanase expression in acute myeloid leukemia cells  

SciTech Connect

Heparanase is a heparan sulfate-degrading endoglycosidase expressed by mature monocytes and myeloid cells, but not by immature hematopoietic progenitors. Heparanase gene expression is upregulated during differentiation of immature myeloid cells. PML-RAR{alpha} and PLZF-RAR{alpha} fusion gene products associated with acute promyelocytic leukemia abrogate myeloid differentiation and heparanase expression. AML-Eto, a translocation product associated with AML FAB M2, also downregulates heparanase gene expression. The common mechanism that underlines the activity of these three fusion gene products involves the recruitment of histone deacetylase complexes to specific locations within the DNA. We found that retinoic acid that dissociates PML-RAR{alpha} from the DNA, and which is used to treat acute promyelocytic leukemia patients, restores heparanase expression to normal levels in an acute promyelocytic leukemia cell line. The retinoic acid effects were also observed in primary acute promyelocytic leukemia cells and in a retinoic acid-treated acute promyelocytic leukemia patient. Histone deacetylase inhibitor reverses the downregulation of heparanase expression induced by the AML-Eto fusion gene product in M2 type AML. In summary, we have characterized a link between leukomogenic factors and the downregulation of heparanase in myeloid leukemic cells.

Eshel, Rinat [Hematology Institute, Sourasky Medical Center, Tel-Aviv (Israel); Ben-Zaken, Olga [Department of Oncology, Hadassah-Hebrew University hospital, Jerusalem (Israel); Vainas, Oded [The Hematology Institute, Sourasky Medical Center, Tel-Aviv (Israel); Nadir, Yona [Department of Hematology, Rambam Medical Center, Haifa (Israel); Minucci, Saverio [European Institute of Oncology, Milan (Italy); Polliack, Aaron [Department of Hematology, Hadassah-Hebrew University hospital, Jerusalem (Israel); Naparstek, Ella [Hematology Institute, Sourasky Medical Center, Tel-Aviv (Israel); Vlodavsky, Israel [Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion, Haifa (Israel); Katz, Ben-Zion [Hematology Institute, Sourasky Medical Center, Tel-Aviv (Israel); Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); E-mail: bkatz@tasmc.healt.gov.il

2005-10-07

98

POSTER PRESENTATION Open Access Recurrent TET2 mutations in adult T cell leukemia  

E-print Network

POSTER PRESENTATION Open Access Recurrent TET2 mutations in adult T cell leukemia Ambroise Marçais1 this article as: Marçais et al.: Recurrent TET2 mutations in adult T cell leukemia. Retrovirology 2014 11(Suppl

Paris-Sud XI, Université de

99

Proteasome inhibitor bortezomib targeted tumor–endothelial cell interaction in T-cell leukemia\\/lymphoma  

Microsoft Academic Search

Endothelial cells have special relevance in tumor progression. Here, we investigated the effect of the proteasome inhibitor\\u000a bortezomib on tumor–endothelial cell interaction in T-cell leukemia\\/lymphoma. In vitro, T-leukemia\\/lymphoma cell lines and\\u000a primary T-leukemia\\/lymphoma cells were cultured with endothelial cells, either together or separately in Millicell Hanging\\u000a Cell Culture system, the latter permits mutual cell exchange. At clinically achievable concentrations, in

Wen-Yu Shi; Li Wang; Dan Xiao; Yin Yao; Fan Yang; Xiao-Xing Jiang; Christophe Leboeuf; Anne Janin; Sai-Juan Chen; Wei-Li Zhao

2011-01-01

100

A novel self-lipid antigen targets human T cells against CD1c+ leukemias  

PubMed Central

T cells that recognize self-lipids presented by CD1c are frequent in the peripheral blood of healthy individuals and kill transformed hematopoietic cells, but little is known about their antigen specificity and potential antileukemia effects. We report that CD1c self-reactive T cells recognize a novel class of self-lipids, identified as methyl-lysophosphatidic acids (mLPAs), which are accumulated in leukemia cells. Primary acute myeloid and B cell acute leukemia blasts express CD1 molecules. mLPA-specific T cells efficiently kill CD1c+ acute leukemia cells, poorly recognize nontransformed CD1c-expressing cells, and protect immunodeficient mice against CD1c+ human leukemia cells. The identification of immunogenic self-lipid antigens accumulated in leukemia cells and the observed leukemia control by lipid-specific T cells in vivo provide a new conceptual framework for leukemia immune surveillance and possible immunotherapy. PMID:24935257

Lepore, Marco; de Lalla, Claudia; Gundimeda, S. Ramanjaneyulu; Gsellinger, Heiko; Consonni, Michela; Garavaglia, Claudio; Sansano, Sebastiano; Piccolo, Francesco; Scelfo, Andrea; Häussinger, Daniel; Montagna, Daniela; Locatelli, Franco; Bonini, Chiara; Bondanza, Attilio; Forcina, Alessandra; Li, Zhiyuan; Ni, Guanghui; Ciceri, Fabio; Jenö, Paul; Xia, Chengfeng

2014-01-01

101

A novel self-lipid antigen targets human T cells against CD1c(+) leukemias.  

PubMed

T cells that recognize self-lipids presented by CD1c are frequent in the peripheral blood of healthy individuals and kill transformed hematopoietic cells, but little is known about their antigen specificity and potential antileukemia effects. We report that CD1c self-reactive T cells recognize a novel class of self-lipids, identified as methyl-lysophosphatidic acids (mLPAs), which are accumulated in leukemia cells. Primary acute myeloid and B cell acute leukemia blasts express CD1 molecules. mLPA-specific T cells efficiently kill CD1c(+) acute leukemia cells, poorly recognize nontransformed CD1c-expressing cells, and protect immunodeficient mice against CD1c(+) human leukemia cells. The identification of immunogenic self-lipid antigens accumulated in leukemia cells and the observed leukemia control by lipid-specific T cells in vivo provide a new conceptual framework for leukemia immune surveillance and possible immunotherapy. PMID:24935257

Lepore, Marco; de Lalla, Claudia; Gundimeda, S Ramanjaneyulu; Gsellinger, Heiko; Consonni, Michela; Garavaglia, Claudio; Sansano, Sebastiano; Piccolo, Francesco; Scelfo, Andrea; Häussinger, Daniel; Montagna, Daniela; Locatelli, Franco; Bonini, Chiara; Bondanza, Attilio; Forcina, Alessandra; Li, Zhiyuan; Ni, Guanghui; Ciceri, Fabio; Jenö, Paul; Xia, Chengfeng; Mori, Lucia; Dellabona, Paolo; Casorati, Giulia; De Libero, Gennaro

2014-06-30

102

?-Arrestin1 promotes the self-renewal of the leukemia-initiating cell-enriched subpopulation in B-lineage acute lymphoblastic leukemia related to DNMT1 activity.  

PubMed

The self-renewal ability of the leukemia initiating cell-enriched subpopulation is critical for leukemia initiation and maintenance. However, the regulation of leukemia initiating cells for the leukemia progression is poorly understood. In this study, we observed that ?-Arrestin1, a multiple-function protein, is elevated in leukemia initiating cells-enriched fraction from B-lineage acute lymphoblastic leukemia patients. The loss of ?-Arrestin1 in leukemia initiating cells-enriched fraction attenuates its self-renewal capacity both in vitro and in vivo. Further experiments showed that the mRNA expression level of ?-Arrestin1 is negatively correlated with that of PTEN in leukemia initiating cells-enriched fraction. Moreover, DNA methylation of the PTEN promoter region, the activity and expression of DNMTs were enhanced in the leukemia initiating cells-enriched fraction. The inhibition of DNMT1 activity impaired the self-renewal and increased expression of PTEN of leukemia initiating cells-enriched fraction. In addition, depletion of ?-Arrestin1 significantly decreased DNMT1 activity and PTEN methylation, and consistently increased PTEN expression in leukemia initiating cells-enriched fraction. Our study reveals a novel function of ?-Arrestin1 in the regulation of the self-renewal of leukemia initiating cells-enriched fraction from B-lineage acute lymphoblastic leukemia patients related to DNMT1 activity, indicating that ?-Arrestin1 is a potential therapeutic target in B-lineage acute lymphoblastic leukemia. PMID:25444908

Shu, Yi; Zhou, Xiaoyan; Qi, Xinkun; Liu, Shan; Li, Kang; Tan, Junjie; Liu, Zhidai; Yu, Jie; Zhang, Penghui; Zou, Lin

2015-02-01

103

NFKB1 Is a Direct Target of the TAL1 Oncoprotein in Human T Leukemia Cells  

E-print Network

NFKB1 Is a Direct Target of the TAL1 Oncoprotein in Human T Leukemia Cells Pei-Yun Chang, 1 Kyle Abstract We recently showed that a subset of human T acute lymphoblastic leukemia (T-ALL) cell lines in CEM T leukemia cells, basal NFKB1 expression is increased, and the levels of p65:cRel complex

Miyamoto, Shigeki

104

Therapy-induced selective loss of leukemia-initiating activity in murine adult T cell leukemia  

PubMed Central

Chronic HTLV-I (human T cell lymphotropic virus type I) infection may cause adult T cell leukemia/lymphoma (ATL), a disease with dismal long-term prognosis. The HTLV-I transactivator, Tax, initiates ATL in transgenic mice. In this study, we demonstrate that an As2O3 and IFN-? combination, known to trigger Tax proteolysis, cures Tax-driven ATL in mice. Unexpectedly, this combination therapy abrogated initial leukemia engraftment into secondary recipients, whereas the primary tumor bulk still grew in the primary hosts, only to ultimately abate later on. This loss of initial transplantability required proteasome function. A similar regimen recently yielded unprecedented disease control in human ATL. Our demonstration that this drug combination targeting Tax stability abrogates tumor cell immortality but not short-term growth may foretell a favorable long-term efficiency of this regimen in patients. PMID:21135137

El Hajj, Hiba; El-Sabban, Marwan; Hasegawa, Hideki; Zaatari, Ghazi; Ablain, Julien; Saab, Shahrazad T.; Janin, Anne; Mahfouz, Rami; Nasr, Rihab; Kfoury, Youmna; Nicot, Christophe; Hermine, Olivier; Hall, William

2010-01-01

105

FMNL1 promotes proliferation and migration of leukemia cells.  

PubMed

The human FMNL1 is expressed predominantly in hematopoietic cells and has been described previously as overexpressed in hematopoietic malignancies. However, it is not known whether FMNL1 contributes to leukemogenesis. Here, we investigate the FMNL1 function using two different human leukemia models: Namalwa and K562 cell lines. FMNL1 depletion reduced cell proliferation and colony formation in both leukemic cell types, as well as a decrease in the tumor growth of FMNL1-depleted Namalwa cell xenografts. In addition, there was a decrease in migration and in TEM in FMNL1-depleted Namalwa cells. FMNL1 endogenously associates with Rac1, and FMNL1 silencing resulted in an increased Rac1 activity. The reduced migration observed in FMNL1-depleted cells was restored by inhibiting Rac activity. Our results indicate that FMNL1 stimulates leukemia cell proliferation as well as migration. This suggests that FMNL1 contributes to leukemogenesis and could act in part through Rac1 regulation. PMID:23801653

Favaro, Patricia; Traina, Fabiola; Machado-Neto, João Agostinho; Lazarini, Mariana; Lopes, Matheus Rodrigues; Pereira, João Kleber Novais; Costa, Fernando Ferreira; Infante, Elvira; Ridley, Anne J; Saad, Sara Teresinha Olalla

2013-09-01

106

Single-cell sphingosine kinase activity measurements in primary leukemia.  

PubMed

Sphingosine kinase (SK) is a promising therapeutic target in a number of cancers, including leukemia. Traditionally, SK has been measured in bulk cell lysates, but this technique obscures the cellular heterogeneity present in this pathway. For this reason, SK activity was measured in single cells loaded with a fluorescent sphingosine reporter. An automated capillary electrophoresis (CE) system enabled rapid separation and quantification of the phosphorylated and nonphosphorylated sphingosine reporter in single cells. SK activity was measured in tissue-cultured cells derived from chronic myelogenous leukemia (K562), primary peripheral blood mononuclear cells (PBMCs) from three patients with different forms of leukemia, and enriched leukemic blasts from a patient with acute myeloid leukemia (AML). Significant intercellular heterogeneity existed in terms of the degree of reporter phosphorylation (as much as an order of magnitude difference), the amount of reporter uptake, and the metabolites formed. In K562 cells, the average amount of reporter converted to the phosphorylated form was 39?±?26% per cell. Of the primary PBMCs analyzed, the average amount of phosphorylated reporter was 16?±?25%, 11?±?26%, and 13?±?23% in a chronic myelogenous leukemia (CML) patient, an AML patient, and a B-cell acute lymphocytic leukemia (B-ALL) patient, respectively. These experiments demonstrated the challenge of studying samples comprised of multiple cell types, with tumor blasts present at 5 to 87% of the cell population. When the leukemic blasts from a fourth patient with AML were enriched to 99% of the cell population, 19?±?36% of the loaded sphingosine was phosphorylated. Thus, the diversity in SK activity remained even in a nearly pure tumor sample. These enriched AML blasts loaded significantly less reporter (0.12?±?0.2 amol) relative to that loaded into the PBMCs in the other samples (?1 amol). The variability in SK signaling may have important implications for SK inhibitors as therapeutics for leukemia and demonstrates the value of single-cell analysis in characterizing the nature of oncogenic signaling in cancer. PMID:24980601

Dickinson, Alexandra J; Hunsucker, Sally A; Armistead, Paul M; Allbritton, Nancy L

2014-11-01

107

Cell-based immune therapy shows promise in leukemia patients  

Cancer.gov

Memorial Sloan-Kettering investigators report that genetically modified immune cells have shown great promise in killing the cancer cells of patients with relapsed B cell acute lymphoblastic leukemia (ALL). In fact, all five of the patients who have received the new therapy – known as targeted immunotherapy – have gone into complete remission, with no detectable cancer cells. The results of this ongoing clinical trial are reported online on March 20 in the journal Science Translational Medicine.

108

Ikaros Induces Quiescence and T-Cell Differentiation in a Leukemia Cell Line  

Microsoft Academic Search

Ikaros is a hematopoietic cell-specific zinc finger DNA binding protein that plays an important role in lymphocyte development. Genetic disruption of Ikaros results in T-cell transformation. Ikaros null mice develop leukemia with 100% penetrance. It has been hypothesized that Ikaros controls gene expression through its association with chromatin remodeling complexes. The development of leukemia in Ikaros null mice suggests that

Katie L. Kathrein; Rachelle Lorenz; Angela Minniti Innes; Erin Griffiths; Susan Winandy

2005-01-01

109

Effects of lentivirus mediated STAT3 silencing on human chronic myeloid leukemia cells and leukemia mice  

PubMed Central

Objective: To investigate the effects of lentivirus mediated STAT3 silencing on human chronic myeloid leukemia cells (K562) and the growth of chronic myeloid leukemia mice as well as to explore the potential mechanisms. Methods: Unbtreated K562 cells (CON), blank lentivirus transfected K562 cells (NC) and K562 cells expressing STAT3 siRNA (STAT3 siRNA) were injected into SCID mice to establish the chronic myeloid leukemia model in mice. The growth, peripheral white blood cell count and spleen index in these mice were determined. Results: In vitro experiment showed, when compared with control group, the interference efficiency of STAT3 expression was as high as 97.5% in K562 cells. Western blot assay revealed that the expression of c-Myc, Bcl-xL and Cyclin D1 reduced by 17.01%, 7.3% and 6.82%, respectively, showing significant difference when compared with control group (P < 0.01). These findings were consistent with those from fluorescence quantitative PCR. In vivo experiment showed the body weight of mice reduced progressively and the peripheral white blood cell count increased gradually in control group, accompanied by dragging hind limbs and progressive enlargement of the spleen. The body weight remained unchanged, peripheral white blood cell count reduced gradually and the spleen did not enlarge in mice treated with STAT3 siRNA expressing cells. Conclusion: Lentivirus mediated STAT3 silencing may inhibit the expression of its downstream genes (c-Myc, Bcl-xL and Cyclin D1) related to cell proliferation, apoptosis and cycle to suppress the malignant biological behaviors, and STAT3 silencing also inhibit the leukemogenic potency of K562 cells in mice. PMID:25550912

Jia, Xinyan; Yang, Wenzhong; Han, Jia; Xiong, Hong

2014-01-01

110

SERUM-MEDIATED LEUKEMIA CELL DESTRUCTION IN AKR MICE  

PubMed Central

AKR mice with spontaneous leukemia were infused with normal serum from a variety of species. Leukemia cell destruction was produced by serum from strains of mice possessing the full spectrum of complement components, but not by serum from strains with a genetically determined deficiency of C5. Serum from guinea pigs, horses, and humans also causes destruction of leukemia cells. The antileukemic factor in normal serum was heat labile (56°C for 35 min) and could be inactivated by cobra venom factor (CVF). Tests of individual complement factors from guinea pig serum and from human serum suggest that C5 is the antileukemic complement component in normal serum. Evidence was obtained that complement also plays a role in the antileukemic effect of interferon and endotoxin. PMID:4744012

Kassel, Robert L.; Old, Lloyd J.; Carswell, Elizabeth A.; Fiore, Nancy C.; Hardy, William D.

1973-01-01

111

[Allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia].  

PubMed

This study was purposed to explore the therapeutic efficacy and influencing factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with chronic myelomonocytic leukemia (CMML) and in patients with juvenile myelomonocytic leukemia (JMML). The clinical data of 3 cases of CMML and 2 cases of JMML underwent allo-HSCT were analysed in term of multiparameter. The results showed that the hematopoietic stem cells in 5 patients grafted successfully. One case of JMML died of pulmonary disease, other 4 cases survive without disease. The analysis found that the disease burden before transplant, chromosome karyotype, acute GVHD II-IV and poor risk cytogenetics all associated with the relapse rate and disease-free survival rate of CMML. The low intensity conditioning regimen was better than myeloablative conditioning regimen. Type of donor and source of stem cells did not statistically and significantly affect OS and RFS. The splenectomy before allo-HSCT as well as spleen size at time of the alloHSCT did not influence on posttransplantation outcome of JMML. However, cord blood HSCT for JMML patients delayed hematologic recovery as compared to that of bone marrow or peripheral blood HSCT. The age, GVHD, HbF level played an important role in leukemia replace. It is concluded that the allogeneic hematopoietic stem cell transplantation is a curative regimen for CMML and JMML, but there also is a serial problems to be resolved. PMID:25130828

Shao, Qun; Wang, Zhi-Dong; Zheng, Xiao-Li; Dong, Lei; Han, Dong-Mei; Yan, Hong-Ming; Wang, Heng-Xiang; Duan, Lian-Ning

2014-08-01

112

Identification and targeting leukemia stem cells: The path to the cure for acute myeloid leukemia  

PubMed Central

Accumulating evidence support the notion that acute myeloid leukemia (AML) is organized in a hierarchical system, originating from a special proportion of leukemia stem cells (LSC). Similar to their normal counterpart, hematopoietic stem cells (HSC), LSC possess self-renewal capacity and are responsible for the continued growth and proliferation of the bulk of leukemia cells in the blood and bone marrow. It is believed that LSC are also the root cause for the treatment failure and relapse of AML because LSC are often resistant to chemotherapy. In the past decade, we have made significant advancement in identification and understanding the molecular biology of LSC, but it remains a daunting task to specifically targeting LSC, while sparing normal HSC. In this review, we will first provide a historical overview of the discovery of LSC, followed by a summary of identification and separation of LSC by either cell surface markers or functional assays. Next, the review will focus on the current, various strategies for eradicating LSC. Finally, we will highlight future directions and challenges ahead of our ultimate goal for the cure of AML by targeting LSC. PMID:25258669

Zhou, Jianbiao; Chng, Wee-Joo

2014-01-01

113

Nilotinib and Imatinib Mesylate After Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia  

ClinicalTrials.gov

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

2014-12-09

114

Eradication of Chronic Myeloid Leukemia Stem Cells: A Novel Mathematical Model Predicts No Therapeutic  

E-print Network

Eradication of Chronic Myeloid Leukemia Stem Cells: A Novel Mathematical Model Predicts induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML), yet many patients B, Holyoake T, Michor F (2009) Eradication of Chronic Myeloid Leukemia Stem Cells: A Novel

115

BUTYRIC ACID INCREASES INVASIVENESS OF HL-60 LEUKEMIA CELLS: ROLE OF REACTIVE OXYGEN SPECIES  

E-print Network

1 BUTYRIC ACID INCREASES INVASIVENESS OF HL-60 LEUKEMIA CELLS: ROLE OF REACTIVE OXYGEN SPECIES differentiation of human leukemia, including HL-60 cells. By using a fluorescent probe, we showed that reactive and increased invasiveness. Keywords: butyrate, differentiation, invasion, leukemia, matrix metalloproteinase

Paris-Sud XI, Université de

116

Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors  

PubMed Central

Despite efforts to understand and treat acute myeloid leukemia (AML), there remains a need for more comprehensive therapies to prevent AML-associated relapses. To identify new therapeutic strategies for AML, we screened a library of on- and off-patent drugs and identified the antimalarial agent mefloquine as a compound that selectively kills AML cells and AML stem cells in a panel of leukemia cell lines and in mice. Using a yeast genome-wide functional screen for mefloquine sensitizers, we identified genes associated with the yeast vacuole, the homolog of the mammalian lysosome. Consistent with this, we determined that mefloquine disrupts lysosomes, directly permeabilizes the lysosome membrane, and releases cathepsins into the cytosol. Knockdown of the lysosomal membrane proteins LAMP1 and LAMP2 resulted in decreased cell viability, as did treatment of AML cells with known lysosome disrupters. Highlighting a potential therapeutic rationale for this strategy, leukemic cells had significantly larger lysosomes compared with normal cells, and leukemia-initiating cells overexpressed lysosomal biogenesis genes. These results demonstrate that lysosomal disruption preferentially targets AML cells and AML progenitor cells, providing a rationale for testing lysosomal disruption as a novel therapeutic strategy for AML. PMID:23202731

Sukhai, Mahadeo A.; Prabha, Swayam; Hurren, Rose; Rutledge, Angela C.; Lee, Anna Y.; Sriskanthadevan, Shrivani; Sun, Hong; Wang, Xiaoming; Skrtic, Marko; Seneviratne, Ayesh; Cusimano, Maria; Jhas, Bozhena; Gronda, Marcela; MacLean, Neil; Cho, Eunice E.; Spagnuolo, Paul A.; Sharmeen, Sumaiya; Gebbia, Marinella; Urbanus, Malene; Eppert, Kolja; Dissanayake, Dilan; Jonet, Alexia; Dassonville-Klimpt, Alexandra; Li, Xiaoming; Datti, Alessandro; Ohashi, Pamela S.; Wrana, Jeff; Rogers, Ian; Sonnet, Pascal; Ellis, William Y.; Corey, Seth J.; Eaves, Connie; Minden, Mark D.; Wang, Jean C.Y.; Dick, John E.; Nislow, Corey; Giaever, Guri; Schimmer, Aaron D.

2012-01-01

117

Leukemia . Author manuscript Sirolimus enhances the effect of apoptotic cell infusion on hematopoietic  

E-print Network

Leukemia . Author manuscript Page /1 6 Sirolimus enhances the effect of apoptotic cell infusion not candidate for standard myeloablative AHCT and diseases other than acute leukemia. However, and despite some

Paris-Sud XI, Université de

118

Monoclonal B-Cell Lymphocytosis and Chronic Lymphocytic Leukemia  

Microsoft Academic Search

Background A diagnosis of chronic lymphocytic leukemia (CLL) requires a count of over 5000 circulating CLL-phenotype cells per cubic millimeter. Asymptomatic persons with fewer CLL-phenotype cells have monoclonal B-cell lymphocytosis (MBL). The goal of this study was to investigate the relation between MBL and CLL. Methods We investigated 1520 subjects who were 62 to 80 years of age with a

Andy C. Rawstron; Fiona L. Bennett; Sheila J. M. O'Connor; Marwan Kwok; James A. L. Fenton; Marieth Plummer; Ruth de Tute; Roger G. Owen; Stephen J. Richards; Andrew S. Jack; Peter Hillmen

2008-01-01

119

Adult T-Cell Leukemia-Lymphoma during Pregnancy  

PubMed Central

Adult T-cell leukemia-lymphoma (ATL) is an uncommon highly aggressive T-cell lymphoma associated with human T-cell lymphotropic virus type 1 (HTLV-1) infection. It is rarely encountered during pregnancy and is particularly challenging to treat due to its aggressive nature and because of the lack of robust data on optimal chemotherapy. We report a case of a Jamaican immigrant diagnosed with ATL during pregnancy. PMID:23840994

Olaso, Aedan Simon; Cohen, Seth; Kossev, Plamen

2013-01-01

120

Large-scale production of hairy root.  

PubMed

Many products of interest are synthesized in organized tissues, but not formed in suspension or callus culture. Therefore, most attention has been focused on root cultures. The transgenic plant,"hairy root", has brought us to dramatic improvements in growth rate and high content of desirable products. Since the roots are quite different from callus in morphology, the culture manner should be explored independently. By providing a growth environment, an elite hairy root can be a more attractive plant. Both of strain selection to generate more competent plants in breeding and engineering development are necessary to overcome various limitations. In this chapter the engineering issues involved in using hairy root culture are discussed, as follows. 1. Measurement of cell concentration on line, and a designing bioreactors for hairy root in liquid culture. 2. High cell density culture and its kinetic parameters. 3. Secretion of target products. 4. The micropropagation of the regenerated hairy root by means of artificial seed system. In some cases where callus and suspension culture show negligible productivity, organ culture will be necessary to achieve good formation. This study on hairy root culture indicates one of the best attempts to the recovery of products from the organ culture in plant biotechnology. PMID:15453193

Uozumi, Nobuyuki

2004-01-01

121

Childhood Leukemia  

MedlinePLUS

Leukemia is cancer of the white blood cells. It is the most common type of childhood cancer. ... blood cells help your body fight infection. In leukemia, the bone marrow produces abnormal white blood cells. ...

122

Infusion of stem cells and specially generated T-cells from same donor improves leukemia survival  

Cancer.gov

In a significant advance for harnessing the immune system to treat leukemias, researchers at Fred Hutchinson Cancer Research Center for the first time have successfully infused large numbers of donor T-cells specific for a key anti-leukemic antigen to prolong survival in high-risk and relapsed leukemia patients after stem cell transplantation. Both the stem cells for transplant and the T-cells came from the same matched donors.

123

Systemic mastocytosis: progressive evolution of an occult disease into fatal mast cell leukemia: unique findings on an unusual hematological neoplasm.  

PubMed

Systemic mastocytosis (SM) may be associated with a clonal hematopoietic non-mast cell-lineage disease (AHNMD). SM and AHNMD even may be clonally related. This report contributes to a better understanding of the different morphological aspects of SM by demonstrating that various AHNMDs can be detected in one patient during the course of disease. Routinely processed biopsy specimens of bone marrow and spleen removed from a 63-year-old man were investigated including a broad panel of immunohistochemical stainings. KIT codon 816 mutation analysis was carried out by melting point analysis of nested PCR products amplified from DNA of pooled microdissected mast cells. The histomorphological features of the initial bone marrow showed diffuse infiltration by hairy cell leukemia (HCL). Occult SM was only detected retrospectively by demonstration of a slight diffuse increase in loosely scattered, spindle-shaped mast cells carrying the activating point mutation KIT ( D816V ). In the second bone marrow, core biopsy removed about two years later HCL had been completely eradicated, while a diagnosis of SM-AHNMD with multifocal compact mast cell infiltrates associated with a myeloproliferative neoplasm (MPN) and significant increase in eosinophilic granulocytes was established. The third and last bone marrow biopsy specimen lacked the features of both MPN and HCL but showed progression into a secondary mast cell leukemia (MCL) with a focal sarcomatous component. To the best of the authors' knowledge, this is the first description of a case of SM-AHNMD with coexisting hematological neoplasms of lymphatic and myeloid origin initially presenting as occult disease and terminating as secondary MCL. PMID:22661384

Gülen, T; Sander, B; Nilsson, G; Palmblad, J; Sotlar, K; Horny, H-P; Hägglund, H

2012-12-01

124

Temple scientists target DNA repair to eradicate leukemia stem cells  

Cancer.gov

Despite treatment with imatinib, a successful drug that targets chronic myeloid leukemia (CML), a deadly type of cancer, some patients may continue to be at risk for relapse because a tiny pool of stem cells is resistant to treatment and may even accumulate additional genetic aberrations, eventually leading to disease progression and relapse. These leukemia stem cells are full of genetic errors, loaded with potentially lethal breaks in DNA, and are in a state of constant self-repair. Now, scientists at Temple University School of Medicine (home to the Fox Chase Cancer Center) may have figured out a way to corral this stem cell activity and stunt further cancer development. In a series of experiments in mice with cancer and in cancer cells, they have shown that they can block the process by which leukemia stem cells repair themselves by targeting a particular protein, RAD52, which the cells depend on to fix genetic mistakes. The findings may lead to a new strategy to help overcome drug resistance that hinges on cancer stem cells gone awry.

125

Tacrolimus and Methotrexate With or Without Sirolimus in Preventing Graft-Versus-Host Disease in Young Patients Undergoing Donor Stem Cell Transplant for Acute Lymphoblastic Leukemia in Complete Remission  

ClinicalTrials.gov

B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Graft Versus Host Disease; L1 Childhood Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

2014-01-23

126

Cannabinoids induce incomplete maturation of cultured human leukemia cells  

SciTech Connect

Monocyte maturation markers were induced in cultured human myeloblastic ML-2 leukemia cells after treatment for 1-6 days with 0.03-30 ..mu..M ..delta../sup 9/-tetrahydrocannabinol (THC), the major psychoactive component of marijuana. After a 2-day or longer treatment, 2- to 5-fold increases were found in the percentages of cells exhibiting reactivity with either the murine OKM1 monoclonal antibody of the Leu-M5 monoclonal antibody, staining positively for nonspecific esterase activity, and displaying a promonocyte morphology. The increases in these differentiation markers after treatment with 0.03-1 ..mu..M THC were dose dependent. At this dose range, THC did not cause an inhibition of cell growth. The THC-induced cell maturation was also characterized by specific changes in the patterns of newly synthesized proteins. The THC-induced differentiation did not, however, result in cells with a highly developed mature monocyte phenotype. However, treatment of these incompletely matured cells with either phorbol 12-myristate 13-acetate of 1..cap alpha..,25-dihydroxycholecalciferol, which are inducers of differentiation in myeloid leukemia cells (including ML-2 cells), produced cells with a mature monocyte morphology. The ML-2 cell system described here may be a useful tool for deciphering critical biochemical events that lead to the cannabinoid-induced incomplete cell differentiation of ML-2 cells and other related cell types. Findings obtained from this system may have important implications for studies of cannabinoid effects on normal human bone-marrow progenitor cells.

Murison, G.; Chubb, C.B.H.; Maeda, S.; Gemmell, M.A.; Huberman, E.

1987-08-01

127

Interleukin 1 gene expression in adult T cell leukemia.  

PubMed

The adult T cell leukemia (ATL) is a T cell neoplasm etiologically associated with human T lymphotropic virus type I (HTLV-I) infection. ATL cells often abnormally express interleukin 2 (IL-2) receptors, and ATL patients may show clinical evidence of hypercalcemia, osteolytic bone lesions, or increased bone turnover. Whereas interleukin 1 (IL-1) is not generally recognized as a product of T cells, this cytokine is capable of both altering IL-2 receptor expression and activating osteoclasts. Thus, we investigated the possibility that primary ATL leukemic T cells and HTLV-I-infected long-term ATL cell lines produce IL-1. S1 nuclease protection assays demonstrated that primary leukemic ATL cells from five out of six patients, as well as one patient with T4+ chronic lymphocytic leukemia, contained considerable quantities of IL-1 beta messenger RNA (mRNA) and small amounts of IL-1 alpha mRNA. These primary leukemic T cells also released biologically active IL-1 protein as evaluated in the murine thymocyte comitogenesis bioassay. In contrast to primary tumor cells, four out of six long-term ATL cell lines produced variable amounts of IL-1 alpha mRNA in the absence of detectable IL-1 beta mRNA as measured by S1 nuclease protection. These data demonstrate that IL-1 gene (especially IL-1 beta) expression occurs in many primary HTLV-I-infected leukemic T cells raising the possibility that this mediator may play a role in the pathological changes associated with this leukemia. Also, these studies show that the pattern of IL-1 alpha and IL-1 beta gene expression differs between primary ATL tumor cells and long-term cultured ATL cell lines, indicating an interesting biological difference in these two HTLV-I-infected cell populations. PMID:2887587

Wano, Y; Hattori, T; Matsuoka, M; Takatsuki, K; Chua, A O; Gubler, U; Greene, W C

1987-09-01

128

Cancer Cell The Common Feature of Leukemia-Associated IDH1  

E-print Network

Cancer Cell Article The Common Feature of Leukemia-Associated IDH1 and IDH2 Mutations of patients with cytogenetically normal acute myeloid leukemia (AML). Surprisingly, less than half of cases glioblastomas, and in 8.5% of acute myeloid leukemias (AML) (Mardis et al., 2009; Yan et al., 2009). Mutations

Sharp, Kim

129

Clonal Evolution of Pre-Leukemic Hematopoietic Stem Cells Precedes Human Acute Myeloid Leukemia  

E-print Network

Clonal Evolution of Pre-Leukemic Hematopoietic Stem Cells Precedes Human Acute Myeloid Leukemia Max myeloid leukemia (AML). Using exome sequencing, we identified mutations present in individual AML patients-PAAuthorManuscriptNIH-PAAuthorManuscriptNIH-PAAuthorManuscript #12;INTRODUCTION Acute myeloid leukemia (AML) is an aggressive malignancy of hematopoietic progenitor

Quake, Stephen R.

130

Tumor cell vaccination trial to promote anti-leukemia responses  

Cancer.gov

Chronic lymphocytic leukemia (CLL) is a cancer of the blood and bone marrow that most often affects older adults. CLL responds to bone marrow stem cell transplantation (allo-HSCT); however, the rate of relapse for CLL remains relatively high. A benefit of allo-HSCT is that treatment can result in the development of an anti-tumor response produced by the grafted cells and is associated with a low risk of cancer relapse. In the Journal of Clinical Investigation, researchers at the Dana Farber Cancer Institute in Boston report the results of a clinical trial that tested the effectiveness of vaccination with a CLL patient's own leukemia cells in the development of anti-tumor responses and relapse reduction.

131

Identification of CD34+ and CD34- leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia.  

PubMed

Translocation of the mixed-lineage leukemia (MLL) gene with AF4, AF9, or ENL results in acute leukemia with both lymphoid and myeloid involvement. We characterized leukemia-initiating cells (LICs) in primary infant MLL-rearranged leukemia using a xenotransplantation model. In MLL-AF4 patients, CD34(+)CD38(+)CD19(+) and CD34(-)CD19(+) cells initiated leukemia, and in MLL-AF9 patients, CD34(-)CD19(+) cells were LICs. In MLL-ENL patients, either CD34(+) or CD34(-) cells were LICs, depending on the pattern of CD34 expression. In contrast, in patients with these MLL translocations, CD34(+)CD38(-)CD19(-)CD33(-) cells were enriched for normal hematopoietic stem cells (HSCs) with in vivo long-term multilineage hematopoietic repopulation capacity. Although LICs developed leukemic cells with clonal immunoglobulin heavy-chain (IGH) rearrangement in vivo, CD34(+)CD38(-)CD19(-)CD33(-) cells repopulated recipient bone marrow and spleen with B cells, showing broad polyclonal IGH rearrangement and recipient thymus with CD4(+) single positive (SP), CD8(+) SP, and CD4(+)CD8(+) double-positive (DP) T cells. Global gene expression profiling revealed that CD9, CD32, and CD24 were over-represented in MLL-AF4, MLL-AF9, and MLL-ENL LICs compared with normal HSCs. In patient samples, these molecules were expressed in CD34(+)CD38(+) and CD34(-) LICs but not in CD34(+)CD38(-)CD19(-)CD33(-) HSCs. Identification of LICs and LIC-specific molecules in primary human MLL-rearranged acute lymphoblastic leukemia may lead to improved therapeutic strategies for MLL-rearranged leukemia. PMID:25538041

Aoki, Yuki; Watanabe, Takashi; Saito, Yoriko; Kuroki, Yoko; Hijikata, Atsushi; Takagi, Masatoshi; Tomizawa, Daisuke; Eguchi, Mariko; Eguchi-Ishimae, Minenori; Kaneko, Akiko; Ono, Rintaro; Sato, Kaori; Suzuki, Nahoko; Fujiki, Saera; Koh, Katsuyoshi; Ishii, Eiichi; Shultz, Leonard D; Ohara, Osamu; Mizutani, Shuki; Ishikawa, Fumihiko

2015-02-01

132

Central Memory Enriched T Cells Following Stem Cell Transplant in Treating Patients With Recurrent B-Cell Non-Hodgkin Lymphoma  

ClinicalTrials.gov

Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

2015-01-13

133

Hyoscyamine Biosynthesis in Datura stramonium Hairy Root In Vitro Systems with Different Ploidy Levels  

Microsoft Academic Search

Hyoscyamine biosynthesis in Datura stramonium hairy roots with different ploidy levels was investigated. For the first time, we report that hairy roots undergo endoreduplication\\u000a and therefore consist mainly of cells with doupled sets of chromosomes of primary plant tissues, used for Agrobacterium transformation. The alkaloid profiles of hairy roots obtained from diploid and tetraploid plants were similar in terms of

A. Pavlov; S. Berkov; J. Weber; Th Bley

2009-01-01

134

Survivin Selectively Modulates Genes Deregulated in Human Leukemia Stem Cells  

PubMed Central

ITD-Flt3 mutations are detected in leukemia stem cells (LSCs) in acute myeloid leukemia (AML) patients. While antagonizing Survivin normalizes ITD-Flt3-induced acute leukemia, it also impairs hematopoietic stem cell (HSC) function, indicating that identification of differences in signaling pathways downstream of Survivin between LSC and HSC are crucial to develop selective Survivin-based therapeutic strategies for AML. Using a Survivin-deletion model, we identified 1,096 genes regulated by Survivin in ITD-Flt3-transformed c-kit+, Sca-1+, and lineageneg (KSL) cells, of which 137 are deregulated in human LSC. Of the 137, 124 genes were regulated by Survivin exclusively in ITD-Flt3+ KSL cells but not in normal CD34neg KSL cells. Survivin-regulated genes in LSC connect through a network associated with the epidermal growth factor receptor signaling pathway and falls into various functional categories independent of effects on apoptosis. Pathways downstream of Survivin in LSC that are distinct from HSC can be potentially targeted for selective anti-LSC therapy. PMID:21253548

Fukuda, Seiji; Abe, Mariko; Onishi, Chie; Taketani, Takeshi; Purevsuren, Jamiyan; Yamaguchi, Seiji; Conway, Edward M.; Pelus, Louis M.

2011-01-01

135

Metnase mediates chromosome decatenation in acute leukemia cells  

PubMed Central

After DNA replication, sister chromatids must be untangled, or decatenated, before mitosis so that chromatids do not tear during anaphase. Topoisomerase II? (Topo II?) is the major decatenating enzyme. Topo II? inhibitors prevent decatenation, causing cells to arrest during mitosis. Here we report that acute myeloid leukemia cells fail to arrest at the mitotic decatenation checkpoint, and their progression through this checkpoint is regulated by the DNA repair component Metnase (also termed SETMAR). Metnase contains a SET histone methylase and transposase nuclease domain, and is a component of the nonhomologous end-joining DNA double-strand break repair pathway. Metnase interacts with Topo II? and enhances its decatenation activity. Here we show that multiple types of acute leukemia cells have an attenuated mitotic arrest when decatenation is inhibited and that in an acute myeloid leukemia (AML) cell line this is mediated by Metnase. Of further importance, Metnase permits continued proliferation of these AML cells even in the presence of the clinical Topo II? inhibitor VP-16. In vitro, purified Metnase prevents VP-16 inhibition of Topo II? decatenation of tangled DNA. Thus, Metnase expression levels may predict AML resistance to Topo II? inhibitors, and Metnase is a potential therapeutic target for small molecule interference. PMID:19458360

Wray, Justin; Williamson, Elizabeth A.; Sheema, Sheema; Lee, Suk-Hee; Libby, Edward; Willman, Cheryl L.; Nickoloff, Jac A.

2009-01-01

136

Immune Response After Stem Cell Transplant in HIV-Positive Patients With Hematologic Cancer  

ClinicalTrials.gov

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV Infection; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

2014-11-17

137

B-cell leukemia/lymphoma panel  

MedlinePLUS

B lymphocyte cell surface markers ... sample is needed. In some cases, white blood cells are removed during a bone marrow biopsy . The ... to a laboratory, where a specialist checks the cell type and characteristics. This procedure is called immunophenotyping. ...

138

Recent advances in acute myeloid leukemia stem cell biology  

PubMed Central

The existence of cancer stem cells has long been postulated, but was proven less than 20 years ago following the demonstration that only a small sub-fraction of leukemic cells from acute myeloid leukemia patients were able to propagate the disease in xenografts. These cells were termed leukemic stem cells since they exist at the apex of a loose hierarchy, possess extensive self-renewal and the ability to undergo limited differentiation into leukemic blasts. Acute myeloid leukemia is a heterogeneous condition at both the phenotypic and molecular level with a variety of distinct genetic alterations giving rise to the disease. Recent studies have highlighted that this heterogeneity extends to the leukemic stem cell, with this dynamic compartment evolving to overcome various selection pressures imposed upon it during disease progression. The result is a complex situation in which multiple pools of leukemic stem cells may exist within individual patients which differ both phenotypically and molecularly. Since leukemic stem cells are thought to be resistant to current chemotherapeutic regimens and mediate disease relapse, their study also has potentially profound clinical implications. Numerous studies have generated important recent advances in the field, including the identification of novel leukemic stem cell-specific cell surface antigens and gene expression signatures. These tools will no doubt prove invaluable for the rational design of targeted therapies in the future. PMID:22511496

Horton, Sarah J.; Huntly, Brian J.P.

2012-01-01

139

Leukemia  

NSDL National Science Digital Library

This patient education program explains what leukemia is and reviews the causes, symptoms, diagnosis, and treatment options. This resource is a MedlinePlus Interactive Health Tutorial from the National Library of Medicine, designed and developed by the Patient Education Institute. NOTE: This tutorial requires a special Flash plug-in, version 4 or above. If you do not have Flash, you will be prompted to obtain a free download of the software before you start the tutorial. You will also need an Acrobat Reader, available as a free download, in order to view the Reference Summary.

Patient Education Institute

140

Chronic mast cell leukemia: a novel leukemia-variant with distinct morphological and clinical features.  

PubMed

Mast cell leukemia (MCL) is a rare form of systemic mastocytosis characterized by leukemic expansion of mostly immature mast cells, organ damage, drug-resistance, and a poor prognosis. Even when treated with chemotherapy, most patients have a life-expectancy of less than one year. However, there are rare patients with MCL in whom the condition is less aggressive and does not cause organ damage within a short time. In these patients, mast cells exhibit a more mature morphology when compared to acute MCL. A recently proposed classification suggests that these cases are referred to as chronic MCL. In the present article, we discuss clinical, histopathological and morphological aspects of acute and chronic MCL. PMID:25443885

Valent, Peter; Sotlar, Karl; Sperr, Wolfgang R; Reiter, Andreas; Arock, Michel; Horny, Hans-Peter

2015-01-01

141

Leukemia-induced phenotypic and functional defects in natural killer cells predict failure to achieve remission in acute myeloid leukemia  

PubMed Central

The majority of patients with acute myeloid leukemia will relapse, and older patients often fail to achieve remission with induction chemotherapy. We explored the possibility that leukemic suppression of innate immunity might contribute to treatment failure. Natural killer cell phenotype and function was measured in 32 consecutive acute myeloid leukemia patients at presentation, including 12 achieving complete remission. Compared to 15 healthy age-matched controls, natural killer cells from acute myeloid leukemia patients were abnormal at presentation, with downregulation of the activating receptor NKp46 (P=0.007) and upregulation of the inhibitory receptor NKG2A (P=0.04). Natural killer cells from acute myeloid leukemia patients had impaired effector function against autologous blasts and K562 targets, with significantly reduced CD107a degranulation, TNF-? and IFN-? production. Failure to achieve remission was associated with NKG2A overexpression and reduced TNF-? production. These phenotypic and functional abnormalities were partially restored in the 12 patients achieving remission. In vitro co-incubation of acute myeloid leukemia blasts with natural killer cells from healthy donors induced significant impairment in natural killer cell TNF-? and IFN-? production (P=0.02 and P=0.01, respectively) against K562 targets and a trend to reduced CD107a degranulation (P=0.07). Under transwell conditions, the inhibitory effect of AML blasts on NK cytotoxicity and effector function was still present, and this inhibitory effect was primarily mediated by IL-10. These results suggest that acute myeloid leukemia blasts induce long-lasting changes in natural killer cells, impairing their effector function and reducing the competence of the innate immune system, favoring leukemia survival. PMID:24488563

Stringaris, Kate; Sekine, Takuya; Khoder, Ahmad; Alsuliman, Abdullah; Razzaghi, Bonnie; Sargeant, Ruhena; Pavlu, Jiri; Brisley, Gill; de Lavallade, Hugues; Sarvaria, Anushruthi; Marin, David; Mielke, Stephan; Apperley, Jane F.; Shpall, Elizabeth J.; Barrett, A. John; Rezvani, Katayoun

2014-01-01

142

Safety and Tolerability Study of PCI-32765 in B Cell Lymphoma and Chronic Lymphocytic Leukemia  

ClinicalTrials.gov

B-cell Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Well-differentiated Lymphocytic Lymphoma; B Cell Lymphoma; Follicular Lymphoma,; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Waldenstrom Macroglobulinemia; Burkitt Lymphoma; B-Cell Diffuse Lymphoma

2013-10-30

143

Inhibition of tumor cell proliferation and induction of apoptosis in human lung carcinoma 95-D cells by a new sesquiterpene from hairy root cultures of Artemisia annua.  

PubMed

Artemisia annua is a rich source of many bioactive substances, and in our recent work, a new sesquiterpene, (Z)-7-acetoxy-methyl-11-methyl-3-methylene-dodeca-1,6,10-triene (AMDT), was isolated and identified from hairy roots culture of A. annua, and its bioactivity was characterized in this work. AMDT showed moderate cytotoxic activities against the human tumor cell lines of HO8910 (ovary), 95-D (lung), QGY (liver) and HeLa (cervix) by MTT assay, whose IC(50) values were ranged within 52.44-73.3 microM. As lung cancer is the No. 1 killer of global cancer patients, our interest is to investigate the ability of AMDT in inducing apoptosis of 95-D tumor cells. The 95-D cell growth was inhibited by AMDT, and the flow cytometry analysis showed its cell cycle was arrested in the G1 phase. The apoptotic rate of the cells increased in a dose-dependent manner. AMDT lowered the mitochondrial membrane potential and increased the expression of caspase-9 and -3. These results revealed that AMDT could efficiently induce 95-D cell apoptosis through mitochondrial dependent pathway, and it may be a potential chemotherapeutic agent. PMID:20362422

Zhai, D-D; Supaibulwatana, K; Zhong, J-J

2010-09-01

144

Relation of Gene Expression Phenotype to Immunoglobulin Mutation Genotype in B Cell Chronic Lymphocytic Leukemia  

Microsoft Academic Search

The most common human leukemia is B cell chronic lymphocytic leukemia (CLL), a malig- nancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising

Andreas Rosenwald; Ash A. Alizadeh; George Widhopf; Richard Simon; R. Eric Davis; Xin Yu; Liming Yang; Oxana K. Pickeral; Laura Z. Rassenti; John Powell; David Botstein; John C. Byrd; Michael R. Grever; Bruce D. Cheson; Nicholas Chiorazzi; Wyndham H. Wilson; Thomas J. Kipps; Patrick O. Brown; Louis M. Staudt

2001-01-01

145

Restoration of WNT4 inhibits cell growth in leukemia-derived cell lines  

PubMed Central

Background WNT signaling pathways are significantly altered during cancer development. Vertebrates possess two classes of WNT signaling pathways: the “canonical” WNT/?-catenin signaling pathway, and the “non-canonical” pathways including WNT/Ca2+ and WNT/Planar cell polarity [PCP] signaling. WNT4 influences hematopoietic progenitor cell expansion and survival; however, WNT4 function in cancer development and the resulting implications for oncogenesis are poorly understood. The aim of this study was twofold: first, to determine the expression of WNT4 in mature peripheral blood cells and diverse leukemia-derived cells including cell lines from hematopoietic neoplasms and cells from patients with leukemia; second, to identify the effect of this ligand on the proliferation and apoptosis of the blast-derived cell lines BJAB, Jurkat, CEM, K562, and HL60. Methods We determined WNT4 expression by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in peripheral blood mononuclear cells (PBMCs) and T- and B-lymphocytes from healthy individuals, as well as from five leukemia-derived cell lines and blasts derived from patients with leukemia. To analyze the effect of WNT4 on cell proliferation, PBMCs and cell lines were exposed to a commercially available WNT4 recombinant human protein. Furthermore, WNT4 expression was restored in BJAB cells using an inducible lentiviral expression system. Cell viability and proliferation were measured by the addition of WST-1 to cell cultures and counting cells; in addition, the progression of the cell cycle and the amount of apoptosis were analyzed in the absence or presence of WNT4. Finally, the expression of WNT-pathway target genes was measured by qRT-PCR. Results WNT4 expression was severely reduced in leukemia-derived cell lines and blasts derived from patients with leukemia. The exposure of cell lines to WNT4 recombinant protein significantly inhibited cell proliferation; inducing WNT4 expression in BJAB cells corroborated this observation. Interestingly, restoration of WNT4 expression in BJAB cells increased the accumulation of cells in G1 phase, and did not induce activation of canonical WNT/?-catenin target genes. Conclusions Our findings suggest that the WNT4 ligand plays a role in regulating the cell growth of leukemia-derived cells by arresting cells in the G1 cell cycle phase in an FZD6-independent manner, possibly through antagonizing the canonical WNT/?-catenin signaling pathway. PMID:24274766

2013-01-01

146

Circulating endothelial cells in patients with chronic lymphocytic leukemia  

Microsoft Academic Search

Angiogenesis is increased in B-cell chronic lymphocytic leukemia (B-CLL). We wanted to quantify and characterize the circulating\\u000a endothelial cells (CECs) in patients with B-CLL and correlate with plasma angiogenesis-related factors. Using a four-color\\u000a flow cytometry, we prospectively analyzed the CEC in the whole blood of 20 healthy controls and 20 patients with B-CLL. We\\u000a quantified (CD45?\\/CD31+\\/CD146+) and characterized the CECs

Ronald S. Go; Dean A. Jobe; Krista E. Asp; Steven M. Callister; Michelle A. Mathiason; Lori A. Meyer; Wayne A. Bottner; Craig E. Cole; John P. Farnen; Kathleen A. Frisby

2008-01-01

147

A pediatric case of T-cell prolymphocytic leukemia.  

PubMed

T-cell Prolymphocytic Leukemia (T-PLL) is a rare entity, and to date has never been reported in children. Here, we describe the first pediatric case of T-PLL in a 16-year old male and review his clinical course through treatment. He underwent therapy with alemtuzumab and pentostatin, which was successful in inducing initial remission. He then underwent an allogeneic matched sibling stem cell transplant following a myeloablative conditioning regimen and remains disease-free 1.5 years after diagnosis. Pediatr Blood Cancer 2015;62:1061-1062. © 2014 Wiley Periodicals, Inc. PMID:25417638

Mitton, Bryan; Coutre, Steven; Willert, Jennifer; Schlis, Krysta; Porteus, Matthew; Kharbanda, Sandhya; Agarwal-Hashmi, Rajni

2015-06-01

148

Cytotoxicity of (-)-vitisin B in human leukemia cells.  

PubMed

Vitis thunbergii var. taiwaniana (VTT) is an indigenous Taiwanese wild grape and is used as a folk medicine in Taiwan. VTT is rich in polyphenols, especially quercetin and resveratrol derivatives, which were demonstrated to exhibit inhibitory activities against carcinogenesis and prevent some neurodegenerative diseases. (-)-Vitisin B is one of the resveratrol tetramers extracted from VTT. In this study, we investigated the mechanisms of (-)-vitisin B on the induction of apoptosis in human HL-60 promyelocytic leukemia cells. First, (-)-vitisin B significantly inhibited cell proliferation through inducing cell apoptosis. This effect appeared to occur in a time- and dose-dependent manner. Cell-cycle distribution was also examined, and we found that (-)-vitisin B significantly induced a sub-G1 population in a dose-dependent manner. In addition, (-)-vitisin B exhibited stronger inhibitory effects on cell proliferation than resveratrol. Second, (-)-vitisin B dose dependently induced apoptosis-related protein expressions, such as the cleavage form of caspase-3, caspase-8, caspase-9, poly(ADP ribose) polymerase, and the proapoptotic Bax protein. Third, (-)-vitisin B treatment also resulted in increases in c-Jun N-terminal kinase (JNK) phosphorylation and Fas ligand (FasL) expression. Moreover, the (-)-vitisin B-induced FasL expression and caspase-3 activation could be reversed by a JNK inhibitor. These results suggest that (-)-vitisin B-induced apoptosis of leukemia cells might be mediated through activation of JNK and Fas death-signal transduction. PMID:23030068

Wu, Shing-Sheng; Chen, Lih-Geeng; Lin, Ren-Jye; Lin, Shyr-Yi; Lo, Yueh-E; Liang, Yu-Chih

2013-07-01

149

Troglitazone Inhibits Cell Growth and Induces Apoptosis of B-Cell Acute Lymphoblastic Leukemia Cells with t(14;18)  

Microsoft Academic Search

Peroxisome proliferator-activated receptor-? (PPAR?), a member of the nuclear receptor superfamily, has been detected in several human leukemia cells. Recent studies reported that PPAR? ligands inhibit cell proliferation and induce apoptosis in both normal and malignant B-lineage cells. We investigated the expression of PPAR? and the effects of PPAR? ligands on UTree-O2, Bay91 and 380, three B-cell acute lymphoblastic leukemia

M. Takenokuchi; K. Saigo; Y. Nakamachi; S. Kawano; M. Hashimoto; T. Fujioka; T. Koizumi; E. Tatsumi; S. Kumagai

2006-01-01

150

[Plasma cell leukemia: three case-reports and review of literature].  

PubMed

Plasma cell leukemia (LP) is a rare hematologic malignancy. Its prognosis is very derogatory. It is defined by the presence in circulating blood of more than 2 G/L plasmocytes or greater than 20% of the total leukocytes. It comes in two forms: secondary plasma cell leukemia complicating multiple myeloma (MM) and primary setting. Its incidence is estimated at 0.9% of patients with acute leukemia and 2-4% of patients with MM. We report, through three observations, the clinical presentation of the plasma cell leukemia, its cytological features, immunophenotypic, physiopathological and therapeutic care. PMID:24342791

Eddou, Hicham; Mahtat, El Mehdi; Zahid, Hamid; Maaroufi, Hicham El; Jennane, Selim; Messaoudi, Nezha; Doghmi, Kamal; Mikdame, Mohamed

2013-01-01

151

Is trisomy cause or consequence of murine T cell leukemia development? Studies on Robertsonian translocation mice.  

PubMed Central

Trypsin-Giemsa banding studies on T cell leukemias induced in Robertsonian translocation mice by dimethylbenz[a]anthracene and Moloney leukemia virus show a trisomy of chromosome 15 even in cases in which chromosome 15 has undergone centromeric fusion with chromosomes 1, 5, or 6. These results suggest that the duplication of gene(s) located on chromosome 15 is of critical importance for murine T cell leukemia development. Images PMID:316545

Spira, J; Wiener, F; Ohno, S; Klein, G

1979-01-01

152

Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer  

ClinicalTrials.gov

Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

2014-06-24

153

Bioactive Actions of Pomegranate Fruit Extracts on Leukemia Cell Lines In Vitro Hold Promise for New Therapeutic Agents for Leukemia  

Microsoft Academic Search

Studies suggest that pomegranates contain bioactive chemicals with potential for treatment and prevention of cancer. Pomegranate juice extracts (PJE) have been shown to inhibit cellular proliferation and tumor growth and induce cell death via apoptosis in a number of cancer cell lines. However, to date, few studies have investigated the potential of PJE in the treatment of leukemia. We investigated

Haytham Dahlawi; Nicola Jordan-Mahy; Malcolm R. Clench; Christine L. Le Maitre

2011-01-01

154

Bioactive Actions of Pomegranate Fruit Extracts on Leukemia Cell Lines In Vitro Hold Promise for New Therapeutic Agents for Leukemia  

Microsoft Academic Search

Studies suggest that pomegranates contain bioactive chemicals with potential for treatment and prevention of cancer. Pomegranate juice extracts (PJE) have been shown to inhibit cellular proliferation and tumor growth and induce cell death via apoptosis in a number of cancer cell lines. However, to date, few studies have investigated the potential of PJE in the treatment of leukemia. We investigated

Haytham Dahlawi; Nicola Jordan-Mahy; Malcolm R. Clench; Christine L. Le Maitre

2012-01-01

155

Snapshot of Leukemia  

MedlinePLUS

... leukemia ( T-ALL ), suggesting therapeutic potential in patients. Published January 2014. [ PubMed Abstract ] DNA sequencing of hairy ... MEK1, suggesting potential new treatment strategies targeting MEK1. Published January 2014. [ PubMed Abstract ] A methylation “signature” (chemical ...

156

Method for differential diagnosis of T cell leukemias using monoclonal antibodies  

SciTech Connect

This patent describes monoclonal antibody 3-3 (HB8369) and 3-40 (HB8368) not capable of immunological reaction with normal, human peripheral T or B blood cell antigens, normal human thymocyte antigens or normal, human bone marrow precursor cell antigens but capable of immunological reaction with separate and distinct T-ALL leukemia antigens (T-ALL) having molecular weights of approximately 35-40,000 KD. The monoclonal antibodies are capable of distinguishing T-ALL leukemia from cutaneous T-cell lymphoma (CTCL), adult T cell leukemia (ATL) and T-cell chronic lymphocytic leukemia (T-CLL) and are further capable of subsetting T-ALL leukemia into E-Rosette positive and E-Rosette negative cells.

Knowles, R.W.; Dupont, B.; Naito, K.; Morishima, Y.

1987-02-24

157

Cytostasis of tumor cell lines by promyelocytic leukemia cell line HL60 differentiated to granulocyte lineage  

Microsoft Academic Search

The human promyelocytic leukemia cell line HL60, when cultured in medium containing dimethyl sulfoxide (DMSO) or granulocyte colonystimulating factor (G-CSF), stopped dividing and differentiated into cells with granulocyte characteristics. We found that differentiated HL60 cells have no detectable cytolytic activity against cultured human bladder cell line (T24 cell), as measured by release of (3H) thymidine, or against K562 cells, as

T. Hara; T. Umeda; T. Niijima; T. Okabe

1985-01-01

158

Divergent effects of supraphysiologic Notch signals on leukemia stem cells and hematopoietic stem cells  

PubMed Central

The leukemia stem cell (LSC) hypothesis proposes that a subset of cells in the bulk leukemia population propagates the leukemia. We tested the LSC hypothesis in a mouse model of Notch-induced T-cell acute lymphoblastic leukemia (T-ALL) in which the tumor cells were largely CD4+CD8+ T cells. LSC activity was enriched but rare in the CD8+CD4?HSAhi immature single-positive T-cell subset. Although our murine T-ALL model relies on transduction of HSCs, we were unable to isolate Notch-activated HSCs to test for LSC activity. Further analysis showed that Notch activation in HSCs caused an initial expansion of hematopoietic and T-cell progenitors and loss of stem cell quiescence, which was followed by progressive loss of long-term HSCs and T-cell production over several weeks. Similar results were obtained in a conditional transgenic model in which Notch activation is induced in HSCs by Cre recombinase. We conclude that although supraphysiologic Notch signaling in HSCs promotes LSC activity in T-cell progenitors, it extinguishes self-renewal of LT-HSCs. These results provide further evidence for therapeutically targeting T-cell progenitors in T-ALL while also underscoring the need to tightly regulate Notch signaling to expand normal HSC populations for clinical applications. PMID:23115273

Shestova, Olga; Xu, Lanwei; Aster, Jon C.

2013-01-01

159

Divergent effects of supraphysiologic Notch signals on leukemia stem cells and hematopoietic stem cells.  

PubMed

The leukemia stem cell (LSC) hypothesis proposes that a subset of cells in the bulk leukemia population propagates the leukemia.We tested the LSC hypothesis in a mouse model of Notch-induced T-cell acute lymphoblastic leukemia (T-ALL) in which the tumor cells were largely CD4+ CD8+ T cells. LSC activity was enriched but rare in the CD8+ CD4 HSA(hi) immature single-positive T-cell subset. Although our murine T-ALL model relies on transduction of HSCs, we were unable to isolate Notch-activated HSCs to test for LSC activity. Further analysis showed that Notch activation in HSCs caused an initial expansion of hematopoietic and T-cell progenitors and loss of stem cell quiescence, which was followed by progressive loss of long-term HSCs and T-cell production over several weeks. Similar results were obtained in a conditional transgenic model in which Notch activation is induced in HSCs by Cre recombinase. We conclude that although supraphysiologic Notch signaling in HSCs promotes LSC activity in T-cell progenitors, it extinguishes self-renewal of LT-HSCs. These results provide further evidence for therapeutically targeting T-cell progenitors in T-ALL while also underscoring the need to tightly regulate Notch signaling to expand normal HSC populations for clinical applications. PMID:23115273

Chiang, Mark Y; Shestova, Olga; Xu, Lanwei; Aster, Jon C; Pear, Warren S

2013-02-01

160

Obatoclax, Fludarabine, and Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia  

ClinicalTrials.gov

B-cell Chronic Lymphocytic Leukemia; Leukemia; Prolymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

2013-09-27

161

Transcriptional Regulation of the Stem Cell Leukemia Gene (SCL) --Comparative Analysis  

E-print Network

Transcriptional Regulation of the Stem Cell Leukemia Gene (SCL) -- Comparative Analysis of Five. Green1 1 Cambridge Institute for Medical Research, Cambridge University, Cambridge, CB2 2XY, United Sanger Institute, Cambridge, CB101SA United Kingdom The stem cell leukemia (SCL) gene encodes a b

Batzoglou, Serafim

162

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma  

ClinicalTrials.gov

Adult T Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Stage II Adult T-Cell Leukemia/Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Contiguous Adult Lymphoblastic Lymphoma; Stage II Non-Contiguous Adult Lymphoblastic Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-Cell Leukemia/Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-Cell Leukemia/Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

2015-04-01

163

PD1\\/PDL1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia\\/lymphoma patients  

Microsoft Academic Search

Adult T-cell leukemia\\/lymphoma (ATLL) develops after infection with human T-cell leukemia virus-1 (HTLV-1) after a long latency period. The negative regulatory programmed death-1\\/programmed death-1 ligand 1 (PD-1\\/PD-L1) pathway has been implicated in the induction of cytotoxic T-lymphocyte (CTL) exhaustion during chronic viral infection along with tumor escape from host immunity. To determine whether the PD-1\\/PD-L1 pathway could be involved in

T Kozako; M Yoshimitsu; H Fujiwara; I Masamoto; S Horai; Y White; M Akimoto; S Suzuki; K Matsushita; K Uozumi; C Tei; N Arima

2009-01-01

164

Leukemia Stem Cells in Personalized Medicine  

PubMed Central

Despite increased comprehension of AML pathogenesis, current treatment strategies have done little to improve upon standard induction chemotherapy to induce long-term remissions. Since the identification of the leukemic stem cell, efforts have been placed on identifying therapeutically actionable pathways that distinguish this increasingly important cellular compartment. With the advent of increased genome sequencing efforts and phenotypic characterization, opportunities for personalized treatment strategies are rapidly emerging. In this review, we highlight recent advances in the understanding of leukemic stem cell biology and their potential for translation into clinically relevant therapeutics. NF-kappa B activation, Bcl-2 expression, oxidative and metabolic state, and epigenetic modifications all bear their own clinical implications. With advancements in genetic, epigenetic, and metabolic profiling, personalized strategies may be feasible in the near future to improve outcomes for AML patients. PMID:24214290

Guzman, Monica L.; Allan, John N.

2015-01-01

165

SET-NUP214 fusion in acute myeloid leukemia- and T-cell acute lymphoblastic leukemia-derived cell lines  

PubMed Central

Background SET-NUP214 fusion resulting from a recurrent cryptic deletion, del(9)(q34.11q34.13) has recently been described in T-cell acute lymphoblastic leukemia (T-ALL) and in one case of acute myeloid leukemia (AML). The fusion protein appears to promote elevated expression of HOXA cluster genes in T-ALL and may contribute to the pathogenesis of the disease. We screened a panel of ALL and AML cell lines for SET-NUP214 expression to find model systems that might help to elucidate the cellular function of this fusion gene. Results Of 141 human leukemia/lymphoma cell lines tested, only the T-ALL cell line LOUCY and the AML cell line MEGAL expressed the SET(TAF-I?)-NUP214 fusion gene transcript. RT-PCR analysis specifically recognizing the alternative first exons of the two TAF-I isoforms revealed that the cell lines also expressed TAF-I?-NUP214 mRNA. Results of fluorescence in situ hybridization (FISH) and array-based copy number analysis were both consistent with del(9)(q34.11q34.13) as described. Quantitative genomic PCR also confirmed loss of genomic material between SET and NUP214 in both cell lines. Genomic sequencing localized the breakpoints of the SET gene to regions downstream of the stop codon and to NUP214 intron 17/18 in both LOUCY and MEGAL cells. Both cell lines expressed the 140 kDa SET-NUP214 fusion protein. Conclusion Cell lines LOUCY and MEGAL express the recently described SET-NUP214 fusion gene. Of special note is that the formation of the SET exon 7/NUP214 exon 18 gene transcript requires alternative splicing as the SET breakpoint is located downstream of the stop codon in exon 8. The cell lines are promising model systems for SET-NUP214 studies and should facilitate investigating cellular functions of the the SET-NUP214 protein. PMID:19166587

Quentmeier, Hilmar; Schneider, Björn; Röhrs, Sonja; Romani, Julia; Zaborski, Margarete; MacLeod, Roderick AF; Drexler, Hans G

2009-01-01

166

Paraptosis Cell Death Induction by the Thiamine Analog Benfotiamine in Leukemia Cells  

PubMed Central

Benfotiamine is a synthetic thiamine analogue that stimulates transketolase, a cellular enzyme essential for glucose metabolism. Currently, benfotiamine is used to treat diabetic neuropathy. We recently reported that oral benfotiamine induced a temporary but remarkable recovery from acute myeloid leukemia in an elderly patient who was ineligible for standard chemotherapy due to dementia and renal failure. In the present study we present evidences that benfotiamine possess antitumor activity against leukemia cells. In a panel of nine myeloid leukemia cell lines benfotiamine impaired the viability of HL-60, NB4, K562 and KG1 cells and also inhibited the growing of primary leukemic blasts. The antitumor activity of benfotiamine is not mediated by apoptosis, necrosis or autophagy, but rather occurs though paraptosis cell death induction. Mechanistic studies revealed that benfotiamine inhibited the activity of constitutively active ERK1/2 and concomitantly increased the phosphorylation of JNK1/2 kinase in leukemic cells. In addition, benfotiamine induced the down regulation of the cell cycle regulator CDK3 which resulted in G1 cell cycle arrest in the sensitive leukemic cells. Moreover, combination index studies showed that benfotiamine enhanced the antiproliferative activities of cytarabine against leukemia cells. These findings suggest that benfotiamine has antitumor therapeutic potential. PMID:25849583

Takami, Akiyoshi; Kondo, Yukio; An, Dao Thi; Sasaki, Motoko; Wakayama, Tomohiko; Nakao, Shinji

2015-01-01

167

[Flow cytometry of bone marrow cells in health, anemias of different etiology and acute leukemias].  

PubMed

The distribution of bone marrow cells by stages of cell cycle was studied by flow cytometry in 26 normal subjects and 107 adult patients (42 with anemias and 65 with acute lymphoblastic or myeloblastic leukemias). Normal myelokaryocyte cell cycle is rather stable, which manifests by low variability of cells. In anemias and, more so, in leukemias the proliferative status of cells varies within a wide range, which is explained by unstable and ineffective hemopoiesis. PMID:9417320

Shmarov, D A; Kuchma, Iu M; Kozinets, G I

1997-10-01

168

Changes in ligno-suberization of cell walls of tomato hairy roots produced by salt treatment: the relationship with the release of a basic peroxidase.  

PubMed

A highly basic peroxidase isoenzyme was shown to be released to the culture medium of tomato (Lycopersicon esculentum) hairy roots grown in Murashige-Skoog (MS) liquid medium when it was supplemented with 100 mM NaCl. In this paper we demonstrate that this enzyme is ionically bound to cell walls and that the release was a consequence of the continuous agitation of the tissue in a high ionic strength medium with salt addition. In order to establish the physiological role of this isoenzyme we partially purified it, and we analysed its kinetic properties as coniferyl alcohol peroxidase. The peroxidase isoenzyme showed a high catalytic efficiency for this substrate, which suggests that it would be associated with the ligno-suberization process. To confirm the involvement of this isoenzyme in that process, we studied the pattern of ligno-suberization of the tissue under different conditions of growth. Our results suggest that this basic peroxidase would be indeed involved in ligno-suberization since its leakage from cell walls, induced by 100 mM NaCl in liquid MS, caused less ligno-suberization of exo and endodermis. On the contrary, more ligno-suberization was seen in cell walls when the hairy roots were grown in a salt-supplemented MS solid medium without contact with it, a condition in which the release of the isoenzyme would be avoided. Thus, through the changes produced by the release of the enzyme from its site of action, we could demonstrate the physiological role of this peroxidase in the processing of root cell walls, being part of control mechanisms of ion and water fluxes through the root. PMID:16616585

Talano, Melina Andrea; Agostini, Elizabeth; Medina, María I; Reinoso, Herminda; Tordable, María del Carmen; Tigier, Horacio A; de Forchetti, Silvia Milrad

2006-05-01

169

Scalarized Hairy Black Holes  

E-print Network

In the presence of a complex scalar field scalar-tensor theory allows for scalarized rotating hairy black holes. We exhibit the domain of existence for these scalarized black holes, which is bounded by scalarized rotating boson stars and ordinary hairy black holes. We discuss the global properties of these solutions. Like their counterparts in general relativity, their angular momentum may exceed the Kerr bound, and their ergosurfaces may consist of a sphere and a ring, i.e., form an ergo-Saturn.

Kleihaus, Burkhard; Yazadjiev, Stoytcho

2015-01-01

170

Scalarized Hairy Black Holes  

E-print Network

In the presence of a complex scalar field scalar-tensor theory allows for scalarized rotating hairy black holes. We exhibit the domain of existence for these scalarized black holes, which is bounded by scalarized rotating boson stars and ordinary hairy black holes. We discuss the global properties of these solutions. Like their counterparts in general relativity, their angular momentum may exceed the Kerr bound, and their ergosurfaces may consist of a sphere and a ring, i.e., form an ergo-Saturn.

Burkhard Kleihaus; Jutta Kunz; Stoytcho Yazadjiev

2015-03-05

171

Ecotropic murine leukemia virus-induced fusion of murine cells  

SciTech Connect

Extensive fusion occurs upon cocultivation of murine fibroblasts producing ecotropic murine leukemia viruses (MuLVs) with a large variety of murine cell lines in the presence of the polyene antibiotic amphotericin B, the active component of the antifungal agent Fungizone. The resulting polykaryocytes contain nuclei from both infected and uninfected cells, as evidenced by autoradiographic labeling experiments in which one or the other parent cell type was separately labeled with (/sup 3/H)thymidine and fused with an unlabeled parent. This cell fusion specifically requires the presence of an ecotropic MuLV-producing parent and is not observed for cells producing xenotropic, amphotropic, or dualtropic viruses. Mouse cells infected with nonecotropic viruses retain their sensitivity toward fusion, whereas infection with ecotropic viruses abrogates the fusion of these cells upon cocultivation with other ecotropic MuLV-producing cells. Nonmurine cells lacking the ecotropic gp70 receptor are not fused under similar conditions. Fusion is effectively inhibited by monospecific antisera to gp70, but not by antisera to p15(E), and studies with monoclonal antibodies identify distinct amino- and carboxy-terminal gp70 regions which play a role in the fusion reaction. The enhanced fusion which occurs in the presence of amphotericin B provides a rapid and sensitive assay for the expression of ecotropic MuLVs and should facilitate further mechanistic studies of MuLV-induced fusion of murine cells.

Pinter, A.; Chen, T.; Lowy, A.; Cortez, N.G.; Silagi, S.

1986-03-01

172

Clonal evolution enhances leukemia propagating cell frequency in T-cell acute lymphoblastic leukemia through Akt/mTORC1 pathway activation  

PubMed Central

SUMMARY Clonal evolution and intratumoral heterogeneity drive cancer progression through unknown molecular mechanisms. To address this issue, functional differences between single T-cell acute lymphoblastic leukemia (T-ALL) clones were assessed using a zebrafish transgenic model. Functional variation was observed within individual clones, with a minority of clones enhancing growth rate and leukemia propagating potential with time. Akt pathway activation was acquired in a subset of these evolved clones, which increased the number of leukemia propagating cells through activating mTORC1, elevated growth rate likely by stabilizing the Myc protein, and rendered cells resistant to dexamethasone, which was reversed by combined treatment with an Akt inhibitor. Thus, T-ALL clones spontaneously and continuously evolve to drive leukemia progression even in the absence of therapy-induced selection. PMID:24613413

Blackburn, Jessica S.; Liu, Sali; Wilder, Jayme L.; Dobrinski, Kimberly P.; Lobbardi, Riadh; Moore, Finola E.; Martinez, Sarah A.; Chen, Eleanor Y.; Lee, Charles; Langenau, David M.

2014-01-01

173

B cell receptor signaling in chronic lymphocytic leukemia  

PubMed Central

BCR signaling plays an important pathogenic role in chronic lymphocytic leukemia (CLL) and B cell lymphomas, based on structural restrictions of the BCR, and BCR-dependent survival and growth of the malignant B cells. In CLL and lymphoma subtypes, ligand-independent (“tonic”) and ligand-dependent BCR signaling have been characterized, which can involve mutations of BCR pathway components or be triggered by (auto-) antigens present in the tissue microenvironment. In CLL, based on high response rates and durable remissions in early-stage clinical trials, there is rapid clinical development of inhibitors targeting BCR-associated kinases (BTK, PI3K?), which will change treatment paradigms in CLL and other B cell malignancies. Here, we discuss the evolution of this field, from BCR-related prognostic markers, to mechanisms of BCR activation, and targeting of BCR-associated kinases, the emerging Achilles’ heel in CLL pathogenesis. PMID:23928062

Burger, Jan A.; Chiorazzi, Nicholas

2013-01-01

174

Insights into the stem cells of chronic myeloid leukemia.  

PubMed

Chronic myeloid leukemia (CML) has long served as a paradigm for generating new insights into the cellular origin, pathogenesis and improved approaches to treating many types of human cancer. Early studies of the cellular phenotypes and genotypes represented in leukemic populations obtained from CML patients established the concept of an evolving clonal disorder originating in and initially sustained by a rare, multipotent, self-maintaining hematopoietic stem cell (HSC). More recent investigations continue to support this model, while also revealing new insights into the cellular and molecular mechanisms that explain how knowledge of CML stem cells and their early differentiating progeny can predict the differing and variable features of chronic phase and blast crisis. In particular, these emphasize the need for new agents that effectively and specifically target CML stem cells to produce non-toxic, but curative therapies that do not require lifelong treatments. PMID:20861912

Sloma, I; Jiang, X; Eaves, A C; Eaves, C J

2010-11-01

175

New strategies in the chemotherapy of leukemia: eradicating cancer stem cells in chronic myeloid leukemia.  

PubMed

Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the Philadelphia-positive chromosome deriving from a translocation between chromosomes 22 and 9. The oncogenic product of this aberrant chromosome is the constitutively active tyrosine kinase BCR-ABL that is responsible for leukemic cell growth, proliferation and survival driven by the dysregulation of a large array of signal transduction pathways. Inhibition of BCR-ABL with tyrosine kinase inhibitors proved to be an efficient therapy of CML in the chronic phase. Unfortunately, the impressive success of BCR-ABL inhibitors as front-line therapy in CML has been tempered by problems of disease persistence or relapse arising from different mechanisms, including mutations in the kinase domain of the enzyme BCRABL and mechanisms independent from BCR-ABL activity. Growing evidence has also suggested a pivotal role of persistent leukemic cancer stem cells, characterized by high self-renewal and pluripotency, in CML maintenance and/or relapse. The present review deals with the most recent advances in this challenging field and focuses on the development of new drugs and therapeutic approaches to eradicate the subtle and dangerous leukemic stem cells responsible for maintaining and sustaining tumor growth. PMID:22414010

Stefanachi, A; Leonetti, F; Nicolotti, O; Catto, M; Pisani, L; Cellamare, S; Altomare, C; Carotti, A

2012-06-01

176

Lenalidomide interferes with tumor-promoting properties of nurse-like cells in chronic lymphocytic leukemia.  

PubMed

Lenalidomide is an immunomodulatory agent clinically active in chronic lymphocytic leukemia patients. The specific mechanism of action is still undefined, but includes modulation of the microenvironment. In chronic lymphocytic leukemia patients, nurse-like cells differentiate from CD14(+) mononuclear cells and protect chronic lymphocytic leukemia cells from apoptosis. Nurse-like cells resemble M2 macrophages with potent immunosuppressive functions. Here, we examined the effect of lenalidomide on the monocyte/macrophage population in chronic lymphocytic leukemia patients. We found that lenalidomide induces high actin polymerization on CD14(+) monocytes through activation of small GTPases, RhoA, Rac1 and Rap1 that correlated with increased adhesion and impaired monocyte migration in response to CCL2, CCL3 and CXCL12. We observed that lenalidomide increases the number of nurse-like cells that lost the ability to nurture chronic lymphocytic leukemia cells, acquired properties of phagocytosis and promoted T-cell proliferation. Gene expression signature, induced by lenalidomide in nurse-like cells, indicated a reduction of pivotal pro-survival signals for chronic lymphocytic leukemia, such as CCL2, IGF1, CXCL12, HGF1, and supported a modulation towards M1 phenotype with high IL2 and low IL10, IL8 and CD163. Our data provide new insights into the mechanism of action of lenalidomide that mediates a pro-inflammatory switch of nurse-like cells affecting the protective microenvironment generated by chronic lymphocytic leukemia into tissues. PMID:25398834

Fiorcari, Stefania; Martinelli, Silvia; Bulgarelli, Jenny; Audrito, Valentina; Zucchini, Patrizia; Colaci, Elisabetta; Potenza, Leonardo; Narni, Franco; Luppi, Mario; Deaglio, Silvia; Marasca, Roberto; Maffei, Rossana

2015-02-01

177

Aberrant Expression of Functional BAFF-System Receptors by Malignant B-Cell Precursors Impacts Leukemia Cell Survival  

PubMed Central

Despite exhibiting oncogenic events, patient's leukemia cells are responsive and dependent on signals from their malignant bone marrow (BM) microenvironment, which modulate their survival, cell cycle progression, trafficking and resistance to chemotherapy. Identification of the signaling pathways mediating this leukemia/microenvironment interplay is critical for the development of novel molecular targeted therapies. We observed that primary leukemia B-cell precursors aberrantly express receptors of the BAFF-system, BAFF-R, BCMA, and TACI. These receptors are functional as their ligation triggers activation of NF-?B, MAPK/JNK, and Akt signaling. Leukemia cells express surface BAFF and APRIL ligands, and soluble BAFF is significantly higher in leukemia patients in comparison to age-matched controls. Interestingly, leukemia cells also express surface APRIL, which seems to be encoded by APRIL-?, a novel isoform that lacks the furin convertase domain. Importantly, we observed BM microenvironmental cells express the ligands BAFF and APRIL, including surface and secreted BAFF by BM endothelial cells. Functional studies showed that signals through BAFF-system receptors impact the survival and basal proliferation of leukemia B-cell precursors, and support the involvement of both homotypic and heterotypic mechanisms. This study shows an unforeseen role for the BAFF-system in the biology of precursor B-cell leukemia, and suggests that the target disruption of BAFF signals may constitute a valid strategy for the treatment of this cancer. PMID:21687682

Maia, Sara; Pelletier, Marc; Ding, Jixin; Hsu, Yen-Ming; Sallan, Stephen E.; Rao, Sambasiva P.; Nadler, Lee M.; Cardoso, Angelo A.

2011-01-01

178

T-cell Depletion of HLA-Identical Transplants in Leukemia  

Microsoft Academic Search

We analyzed the effects of T-cell depletion on the outcome of HLA-identical sibling bone marrow transplants for leukemia by comparing 731 T-cell-depleted transplants with 2,480 non-T-cell-depleted transplants. T-cell depletion decreased acute graft-versus-host disease (GVHD) (relative risk (RR) 0.45; P < .Mol) and chronic GVHD (RR 0.56; P < .Mol). However, it increased graft failure (RR 9.29; P < .OOOl). Leukemia

Alberto M. Marmont; Mary M. Horowitz; Robert Peter Gale; Kathleen Sobocinski; Robert C. Ash; Dirk W. van Bekkum; Richard E. Champlin; Karel A. Dicke; John M. Goldman; Robert A. Good; Roger H. Herzig; Richard Hong; Tohru Masaoka; Alfred A. Rimm; Olle Ringdh; Bruno Speck; Roy S. Weiner; Mortimer M. Bortin

1991-01-01

179

Isolation of Human T-Cell Leukemia Virus in Acquired Immune Deficiency Syndrome (AIDS)  

Microsoft Academic Search

Several isolates of a human type-C retrovirus belonging to one group, known as human T-cell leukemia virus (HTLV), have previously been obtained from patients with adult T-cell leukemia or lymphoma. The T-cell tropism of HTLV and its prevalence in the Caribbean basin prompted a search for it in patients with the epidemic T-cell immune deficiency disorder known as AIDS. Peripheral

Robert C. Gallo; Prem S. Sarin; E. P. Gelmann; Marjorie Robert-Guroff; Ersell Richardson; V. S. Kalyanaraman; Dean Mann; Gurdip D. Sidhu; Rosalyn E. Stahl; Susan Zolla-Pazner; Jacque Leibowitch; Mikulas Popovic

1983-01-01

180

BOVINE LEUKEMIA VIRUS (BLV) SPECIFIC RNA IN INFECTED CELLS T. ASTIER R. MAMOUN B. GUILLEMAIN J.F. DUPLAN  

E-print Network

BOVINE LEUKEMIA VIRUS (BLV) SPECIFIC RNA IN INFECTED CELLS T. ASTIER R. MAMOUN B. GUILLEMAIN J and Baumgartener, 1976). The so-called bovine leukemia virus (BLV) displays morphological and biochemical and virus Fetal lamb kidney cells chronically infected with bovine leukemia virus (FLK-BLV) were kindly

Paris-Sud XI, Université de

181

Targeting FoxM1 transcription factor in T-cell acute lymphoblastic leukemia cell line.  

PubMed

The Forkhead box protein M1 (FoxM1) is an important transcription factor having significant roles in various cellular events. FoxM1 overexpression has been reported to be related with many types of cancer. However, it is not known whether it contributes to oncogenesis of acute lymphoblastic leukemia. Siomycin A, a thiazol antibiotic, is known to inhibit FoxM1 transcriptional activity. In this study, we aimed to determine gene expression levels of FoxM1 in Jurkat cells (T-cell acute lymphoblastic leukemia cell line) and therapeutic potential of targeting FoxM1 by siomycin A alone and in combination with dexamethasone which improves the survival of children with T-cell acute lymphoblastic leukemia (ALL). We also examined the molecular mechanisms of siomycin A and dexamethasone-induced cell death in Jurkat cells. We demonstrated that FoxM1 mRNA is highly expressed in Jurkat cells. Dexamethasone and siomycin A caused a significant reduction in gene expression levels of FoxM1 in Jurkat cells. Targeting FoxM1 by siomycin A and dexamethasone caused a significant decrease in T-ALL cell line proliferation through induction of G1 cell cycle arrest. All these findings suggest a possible role of FoxM1 in T-cell ALL pathogenesis and represent FoxM1 as an attractive target for T-cell ALL therapy. PMID:25557384

Tüfekçi, Özlem; Yand?m, Melis Kartal; Ören, Hale; ?rken, Gülersu; Baran, Yusuf

2015-03-01

182

Leydig cell damage after testicular irradiation for lymphoblastic leukemia  

SciTech Connect

The effect of testicular irradiation on Leydig cell function has been studied in a group of boys irradiated between 1 and 5 years earlier for a testicular relapse of acute lymphoblastic leukemia. Six of the seven boys irradiated during prepubertal life had an absent testosterone response to HCG stimulation. Two of the four boys irradiated during puberty had an appropriate basal testosterone level, but the testosterone response to HCG stimulation was subnormal in three of the four. Abnormalities in gonadotropin secretion consistent with testicular damage were noted in nine of the 11 boys. Evidence of severe Leydig cell damage was present irrespective of whether the boys were studied within 1 year or between 3 and 5 years after irradiation, suggesting that recovery is unlikely. Androgen replacement therapy has been started in four boys and will be required by the majority of the remainder to undergo normal pubertal development.

Shalet, S.M.; Horner, A.; Ahmed, S.R.; Morris-Jones, P.H.

1985-01-01

183

Characterization of resistance to cytosine arabinoside (Ara-C) in NALM-6 human B leukemia cells  

Microsoft Academic Search

BackgroundCytosine arabinoside (1-?-d-arabinofuranosylcytosine;Ara-C) is the most important antimetabolite used for acute leukemia. We established Ara-C (0.003–1 ?mol\\/l)-resistant NALM-6 leukemia cells, and attempted the characterization of their resistance.

Syu-ichi Kanno; Takako Hiura; Takaharu Ohtake; Kimiko Koiwai; Hiroyoshi Suzuki; Mayuko Ujibe; Masaaki Ishikawa

2007-01-01

184

Trial results show high remission rate in leukemia following immune cell therapy  

Cancer.gov

Children and young adults (age 1 to age 30) with chemotherapy-resistant B-cell acute lymphoblastic leukemia (ALL) experienced high remission rates following treatment with an experimental immunotherapy. Results demonstrated that the immunotherapy treatment had anti-leukemia effects in patients and that the treatment was feasible and safe.

185

Positive feedback between NF-?B and TNF-? promotes leukemia-initiating cell capacity  

PubMed Central

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy that originates from leukemia-initiating cells (LICs). The identification of common mechanisms underlying LIC development will be important in establishing broadly effective therapeutics for AML. Constitutive NF-?B pathway activation has been reported in different types of AML; however, the mechanism of NF-?B activation and its importance in leukemia progression are poorly understood. Here, we analyzed myeloid leukemia mouse models to assess NF-?B activity in AML LICs. We found that LICs, but not normal hematopoietic stem cells or non-LIC fractions within leukemia cells, exhibited constitutive NF-?B activity. This activity was maintained through autocrine TNF-? secretion, which formed an NF-?B/TNF-? positive feedback loop. LICs had increased levels of active proteasome machinery, which promoted the degradation of I?B? and further supported NF-?B activity. Pharmacological inhibition of the proteasome complex markedly suppressed leukemia progression in vivo. Conversely, enhanced activation of NF-?B signaling expanded LIC frequency within leukemia cell populations. We also demonstrated a strong correlation between NF-?B activity and TNF-? secretion in human AML samples. Our findings indicate that NF-?B/TNF-? signaling in LICs contributes to leukemia progression and provide a widely applicable approach for targeting LICs. PMID:24382349

Kagoya, Yuki; Yoshimi, Akihide; Kataoka, Keisuke; Nakagawa, Masahiro; Kumano, Keiki; Arai, Shunya; Kobayashi, Hiroshi; Saito, Taku; Iwakura, Yoichiro; Kurokawa, Mineo

2014-01-01

186

Defective immunoregulatory T-cell function in chronic lymphocytic leukemia  

SciTech Connect

Chronic lymphocytic leukemia (CLL) of B-cell origin results in the malignant proliferation of small immunoglobulin-bearing lymphocytes. There is currently a controversy in the literature regarding both the ability of this leukemic population to differentiate into mature plasma cells, as well as the ability of apparently normal T cells from these patients to regulate allogeneic B-cell differentiation. In the present study we have examined the lymphocytes of CLL patients in various clinical stages of their disease and with different surface phenotypes of their leukemic B-cell population. Our results show that leukemic CLL B cells from all 20 patients (including one patient with a monoclonal IgM paraprotein and another with a monoclonal IgG paraprotein) are incapable of further differentiation even in the absence of suppressor T cells and the presence of helper T lymphocytes. This lack of capacity to differentiate is unaffected by clinical stage, by therapy, or by the phenotype of the malignant population. Since the leukemic B population did not suppress normal allogeneic B-cell differentiation, the maturation deficit is evidently intrinsic to the leukemic clone rather than a result of activity of non-T suppressor cells. T helper function was also variably depressed in the blood of some patients with CLL, and this depression did not correlate with clinical stage, with therapy, or with the degree of lymphocytosis. Dysfunction of radiosensitive T suppressor cells was found to be the most consistent regulatory deficit of CLL T cells. Each of 11 patients whose leukemic cell population was of the ..mu..delta, ..mu cap alpha.., or ..mu.. phenotype had both helper and suppressor cell defects.

Han, T.; Ozer, H.; Henderson, E.S.; Dadey, B.; Nussbaum-Blumenson, A.; Barcos, M.

1981-12-01

187

Complete suppression of in vivo growth of human leukemia cells by specific immunotoxins: nude mouse models  

SciTech Connect

In this study, immunotoxins containing monoclonal anti-human T-cell leukemia antibodies are shown to be capable of completely suppressing the tumor growth of human T-cell leukemia cells in vivo without any overt undersirable toxicity. These immunotoxins were prepared by conjugating ricin A chain (RA) with our monoclonal antibodies, SN1 and SN2, directed specifically to the human T-cell leukemia cell surface antigens TALLA and GP37, respectively. The authors have shown that these monoclonal antibodies are highly specific for human T-cell leukemia cells and do not react with various normal cells including normal T and B cells, thymocytes, and bone marrow cells. Ascitic and solid human T-cell leukemia cell tumors were generated in nude mice. The ascitic tumor was generated by transplanting Ichikawa cells (a human T-cell leukemia cell) i.p. into nude mice, whereas the solid tumor was generated by transplanting s.c. MOLT-4 cells (a human T-cell leukemia cell line) and x-irradiated human fibrosarcoma cells into x-irradiated nude mice. To investigate the efficacy of specific immunotoxins in suppression the in vivo growth of the ascitic tumor, they divided 40 nude mice that were injected with Ichikawa cells into four groups. None of the mice in group 4 that were treated with SN1-RA and SN2-RA showed any signs of a tumor or undesirable toxic effects for the 20 weeks that they were followed after the transplantation. Treatment with SN1-RA plus SN2-RA completely suppressed solid tumor growth in 4 of 10 nude mice carrying solid tumors and partially suppressed the tumor growth in the remaining 6 nude mice. These results strongly suggest that SN1-RA and SN2-RA may be useful for clinical treatment.

Hara, H.; Seon, B.K.

1987-05-01

188

Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies  

ClinicalTrials.gov

Acute Myeloid Leukemia/Transient Myeloproliferative Disorder; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Plasmacytoid Dendritic Cell Neoplasm; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies; Waldenström Macroglobulinemia

2014-12-01

189

Childhood Cancer: Leukemia (For Parents)  

MedlinePLUS

About Leukemia The term leukemia refers to cancers of the white blood cells (also called leukocytes or WBCs). When ... the disease without it coming back. Types of Leukemia In general, leukemias are classified into acute (rapidly ...

190

Involvement of tumor necrosis factor (TNF-?) in arsenic trioxide induced apoptotic cell death of murine myeloid leukemia cells  

Microsoft Academic Search

Arsenic trioxide (As2O3) has recently been shown to be effective to inhibit the growth and to induce apoptosis in acute promyelocytic leukemia (APL) but not in acute myeloid leukemia (AML) cells. Recently, we have isolated an As2O3 sensitive subclone JCS-16 from the murine myeloid leukemia WEHI 3B (JCS). At the concentrations of 0.3–3 ?M, As2O3 induces a dose-dependent cytotoxicity and

N. K Mak; R. N. S Wong; K. N Leung; M. C Fung

2002-01-01

191

Ayanin diacetate-induced cell death is amplified by TRAIL in human leukemia cells.  

PubMed

Here we demonstrate that the semi-synthetic flavonoid ayanin diacetate induces cell death selectively in leukemia cells without affecting the proliferation of normal lymphocytes. Incubation of human leukemia cells with ayanin diacetate induced G(2)-M phase cell cycle arrest and apoptosis which was prevented by the non-specific caspase inhibitor z-VAD-fmk and reduced by the overexpression of Bcl-x(L). Ayanin diacetate-induced cell death was found to be associated with: (i) loss of inner mitochondrial membrane potential, (ii) the release of cytochrome c, (iii) the activation of multiple caspases, (iv) cleavage of poly(ADP-ribose) polymerase and (v) the up-regulation of death receptors for TRAIL, DR4 and DR5. Moreover, the combined treatment with ayanin diacetate and TRAIL amplified cell death, compared to single treatments. These results provide a basis for further exploring the potential applications of this combination for the treatment of cancer. PMID:23063980

Marrero, María Teresa; Estévez, Sara; Negrín, Gledy; Quintana, José; López, Mariana; Pérez, Francisco J; Triana, Jorge; León, Francisco; Estévez, Francisco

2012-11-01

192

Myelomastocytic leukemia: myeloid neoplasm characterized by partial differentiation of mast cell-lineage cells.  

PubMed

A novel subtype of myeloid leukemia exhibiting a partial differentiation of mast cell-lineage cells is described. The disease is characterized by an increase in myeloblasts as well as an increase in immature (blast-like) metachromatic cells (>10% in bone marrow or blood smears). Metachromatic cells express KIT (CD117) and tryptase, but lack basophil-related antigens. In contrast to mast cell leukemia/systemic mastocytosis, metachromatic cells do not express CD2 or CD25, do not form multifocal dense aggregates in the bone marrow, and do not exhibit transforming mutations at codon 816 of c-kit. In the few patients recorded so far, a complex karyotype without recurring anomaly was found. The prognosis appears to be grave, although complete remission in response to chemotherapy has been described. PMID:12032870

Valent, Peter; Samorapoompichit, Puchit; Sperr, Wolfgang R; Horny, Hans-Peter; Lechner, Klaus

2002-01-01

193

Targeting acute myeloid leukemia stem cells: a review and principles for the development of clinical trials  

PubMed Central

Despite an increasingly rich understanding of its pathogenesis, acute myeloid leukemia remains a disease with poor outcomes, overwhelmingly due to disease relapse. In recent years, work to characterize the leukemia stem cell population, the disease compartment most difficult to eliminate with conventional therapy and most responsible for relapse, has been undertaken. This, in conjunction with advances in drug development that have allowed for increasingly targeted therapies to be engineered, raises the hope that we are entering an era in which the leukemia stem cell population can be eliminated, resulting in therapeutic cures for acute myeloid leukemia patients. For these therapies to become available, they must be tested in the setting of clinical trials. A long-established clinical trials infrastructure has been employed to shepherd new therapies from proof-of-concept to approval. However, due to the unique features of leukemia stem cells, drugs that are designed to specifically eliminate this population may not be adequately tested when applied to this model. Therefore, in this review article, we seek to identify the relevant features of acute myeloid leukemia stem cells for clinical trialists, discuss potential strategies to target leukemia stem cells, and propose a set of guidelines outlining the necessary elements of clinical trials to allow for the successful testing of stem cell-directed therapies. PMID:25082785

Pollyea, Daniel A.; Gutman, Jonathan A.; Gore, Lia; Smith, Clayton A.; Jordan, Craig T.

2014-01-01

194

Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia  

ClinicalTrials.gov

B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

2014-09-09

195

Alisertib and Romidepsin in Treating Patients With Relapsed or Refractory B-Cell or T-Cell Lymphomas  

ClinicalTrials.gov

Adult B Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Intraocular Lymphoma; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

2015-04-09

196

Glomerulonephritis in chronic lymphocytic leukemia and related B-cell lymphomas  

Microsoft Academic Search

Glomerulonephritis in chronic lymphocytic leukemia and related B-cell lymphomas. We retrospectively analyzed clinical presentation, immunopathological data and renal outcome in 13 patients with glomerulonephritis (GN) and chronic lymphocytic leukemia (CLL) or related diffuse well-differentiated lymphocytic lymphoma (WDLL) of B-cell lineage. B-cell proliferation and glomerulopathy were simultaneously diagnosed in seven of the 13 patients. Nephrotic syndrome was observed in nine patients.

Bruno Moulin; Pierre M Ronco; Beatrice Mougenot; Arnaud Francois; Jean-Paul Fillastre; Francoise Mignon

1992-01-01

197

Transmission of Human T-Cell Leukemia Virus Type 1 to Mice  

Microsoft Academic Search

Human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia\\/lymphoma, HTLV- 1-associated myelopathy\\/tropical spastic paraparesis, and other diseases. For prevention of the transmission of HTLV-1 and manifestation of these diseases, a small-animal model, especially a mouse model, would be useful. We injected HTLV-1-producing T cells (MT-2) intraperitoneally into neonatal C3H\\/HeJ mice. While the antibody against HTLV-1 antigens

JIANHUA FANG; SHIGEKI KUSHIDA; RENQING FENG; MASAKAZU TANAKA; TOMONORI KAWAMURA; HIDEAKI ABE; NAOYOSHI MAEDA; MAKOTO ONOBORI; MITUO HORI; KAZUHIKO UCHIDA; MASANAO MIWA

1998-01-01

198

Acute myelogenous leukemia cells with the MLL-ELL translocation convert morphologically and functionally into adherent myofibroblasts  

SciTech Connect

Bone marrow-myofibroblasts, a major component of bone marrow-stroma, are reported to originate from hematopoietic stem cells. We show in this paper that non-adherent leukemia blasts can change into myofibroblasts. When myeloblasts from two cases of acute myelogenous leukemia with a fusion product comprising mixed lineage leukemia and RNA polymerase II elongation factor, were cultured long term, their morphology changed to that of myofibroblasts with similar molecular characteristics to the parental myeloblasts. The original leukemia blasts, when cultured on the leukemia blast-derived myofibroblasts, grew extensively. Leukemia blasts can create their own microenvironment for proliferation.

Tashiro, Haruko; Mizutani-Noguchi, Mitsuho; Shirasaki, Ryosuke [Department of Hematology/Oncology, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 173-8606 (Japan)] [Department of Hematology/Oncology, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 173-8606 (Japan); Shirafuji, Naoki, E-mail: ramuji@med.teikyo-u.ac.jp [Department of Hematology/Oncology, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 173-8606 (Japan)] [Department of Hematology/Oncology, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 173-8606 (Japan)

2010-01-01

199

Electrospun nanofibers as a bioadhesive platform for capturing adherent leukemia cells.  

PubMed

This study investigated the adhesive behaviors of normal and abnormal hematopoietic cells on nanotopographical materials. Previously, electrospun nanofiber scaffolds (NFSs) were used to capture and expand hematopoietic stem cells in vitro; here, we demonstrate that NFS could also serve as a useful bioadhesive platform for capturing functionally adherent leukemia cells. Collagen-blended poly(d,l-lactide-co-glycolide) NFS enabled more rapid and efficient capture of K562 leukemia cells than tissue culture polystyrene surfaces with up to 70% improved adhesion and shorter time. Cellular extensions, stronger adhesion, and enhanced cell-cell interactions were observed in K562 cells captured on NFS. While NFS promoted hematopoietic progenitor cell proliferation, it inhibited leukemia cell proliferation and affected cell cycle status by shifting more cells toward the G0/G1 phase. The expression of ?-integrins was equally high in both captured and uncaptured leukemia cell populations demonstrating no relation to its adhesive nature. Hematopoietic morphological signatures of NFS captured cells presented no impact on cell differentiation. We conclude that electrospun NFS serves as an excellent platform not only for capturing functionally adherent leukemia cells but also for studying the impact of niche-like structure in the nanoscale. PMID:23536515

Cao, Xue; Kwek, Kenneth; Chan, Jerry K Y; Chan, Casey K H; Lim, Mayasari

2014-02-01

200

Ayanin diacetate-induced cell death is amplified by TRAIL in human leukemia cells  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer Ayanin diacetate as apoptotic inducer in leukemia cells. Black-Right-Pointing-Pointer Cell death was prevented by caspase inhibitors and by the overexpression of Bcl-x{sub L}. Black-Right-Pointing-Pointer The intrinsic and the extrinsic pathways are involved in the mechanism of action. Black-Right-Pointing-Pointer Death receptors are up-regulated and TRAIL enhances apoptotic cell death. -- Abstract: Here we demonstrate that the semi-synthetic flavonoid ayanin diacetate induces cell death selectively in leukemia cells without affecting the proliferation of normal lymphocytes. Incubation of human leukemia cells with ayanin diacetate induced G{sub 2}-M phase cell cycle arrest and apoptosis which was prevented by the non-specific caspase inhibitor z-VAD-fmk and reduced by the overexpression of Bcl-x{sub L}. Ayanin diacetate-induced cell death was found to be associated with: (i) loss of inner mitochondrial membrane potential, (ii) the release of cytochrome c, (iii) the activation of multiple caspases, (iv) cleavage of poly(ADP-ribose) polymerase and (v) the up-regulation of death receptors for TRAIL, DR4 and DR5. Moreover, the combined treatment with ayanin diacetate and TRAIL amplified cell death, compared to single treatments. These results provide a basis for further exploring the potential applications of this combination for the treatment of cancer.

Marrero, Maria Teresa; Estevez, Sara; Negrin, Gledy; Quintana, Jose [Departamento de Bioquimica, Unidad Asociada al Consejo Superior de Investigaciones Cientificas, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria (Spain)] [Departamento de Bioquimica, Unidad Asociada al Consejo Superior de Investigaciones Cientificas, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria (Spain); Lopez, Mariana; Perez, Francisco J.; Triana, Jorge [Departamento de Quimica, Universidad de Las Palmas de Gran Canaria, Instituto Canario de Investigacion del Cancer, 35017 Las Palmas de Gran Canaria (Spain)] [Departamento de Quimica, Universidad de Las Palmas de Gran Canaria, Instituto Canario de Investigacion del Cancer, 35017 Las Palmas de Gran Canaria (Spain); Leon, Francisco [Instituto de Productos Naturales y Agrobiologia, Consejo Superior de Investigaciones Cientificas, Avda. Astrofisico F. Sanchez 3, 38206 La Laguna, Tenerife (Spain)] [Instituto de Productos Naturales y Agrobiologia, Consejo Superior de Investigaciones Cientificas, Avda. Astrofisico F. Sanchez 3, 38206 La Laguna, Tenerife (Spain); Estevez, Francisco, E-mail: festevez@dbbf.ulpgc.es [Departamento de Bioquimica, Unidad Asociada al Consejo Superior de Investigaciones Cientificas, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria (Spain)] [Departamento de Bioquimica, Unidad Asociada al Consejo Superior de Investigaciones Cientificas, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria (Spain)

2012-11-09

201

Hypercalcemic crisis due to adult T cell leukemia: a rare cause of paralytic ileus.  

PubMed

Adult T cell leukemia- lymphoma is a rare aggressive malignancy of the peripheral T lymphocytes, caused by human T cell lymphotropic virus -1 (HTLV-1) infection. Hypercalcemia occurs in about 70% of patients with acute adult T cell leukemia. However, there are very few case reports of adult T cell leukemia presenting as a hypercalcemic crisis. We report a case of a 54-year-old male who presented with abdominal pain, constipation and altered sensorium. On examination he had generalized lymphadenopathy, hepatosplenomegaly and paralytic ileus. Investigation revealed hypercalcemic crisis with low parathormone (PTH) levels. Peripheral smear and bone marrow aspirate were consistent with adult T cell leukemia. HTLV-1 serology was positive. Despite the corrective measures for hypercalcemia and chemotherapy, he succumbed to the illness in a week. PMID:24714244

Kunnathuparambil, Sojan George; Payangappadom, Pradeep Kumar; Yerol, Praveen Kumar; Madhavan, Mukunda; Sreesh, Sreejaya; Narayanan, Premaletha; Devdas, Krishnadas; Ramakrishanan Kattoor, Vinayakumar

2012-01-01

202

Hypercalcemic crisis due to adult T cell leukemia: a rare cause of paralytic ileus  

PubMed Central

Adult T cell leukemia- lymphoma is a rare aggressive malignancy of the peripheral T lymphocytes, caused by human T cell lymphotropic virus -1 (HTLV-1) infection. Hypercalcemia occurs in about 70% of patients with acute adult T cell leukemia. However, there are very few case reports of adult T cell leukemia presenting as a hypercalcemic crisis. We report a case of a 54-year-old male who presented with abdominal pain, constipation and altered sensorium. On examination he had generalized lymphadenopathy, hepatosplenomegaly and paralytic ileus. Investigation revealed hypercalcemic crisis with low parathormone (PTH) levels. Peripheral smear and bone marrow aspirate were consistent with adult T cell leukemia. HTLV-1 serology was positive. Despite the corrective measures for hypercalcemia and chemotherapy, he succumbed to the illness in a week. PMID:24714244

Kunnathuparambil, Sojan George; Payangappadom, Pradeep Kumar; Yerol, Praveen Kumar; Madhavan, Mukunda; Sreesh, Sreejaya; Narayanan, Premaletha; Devdas, Krishnadas; Ramakrishanan Kattoor, Vinayakumar

2012-01-01

203

Flavopiridol in Treating Patients With Chronic Lymphocytic Leukemia  

ClinicalTrials.gov

B-cell Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

2013-01-16

204

Combination Chemotherapy With or Without Rituximab in Treating Younger Patients With Stage III-IV Non-Hodgkin Lymphoma or B-Cell Acute Leukemia  

ClinicalTrials.gov

Childhood B Acute Lymphoblastic Leukemia; Childhood Burkitt Leukemia; Childhood Diffuse Large Cell Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma

2015-01-05

205

CPI-613, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma  

ClinicalTrials.gov

B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

2014-12-02

206

Phosphoinositide-dependent kinase 1 regulates leukemia stem cell maintenance in MLL-AF9-induced murine acute myeloid leukemia.  

PubMed

Although great efforts have been made to improve available therapies, the mortality rate of acute myeloid leukemia (AML) remains high due to poor treatment response and frequent relapse after chemotherapy. Leukemia stem cells (LSCs) are thought to account for this poor prognosis and relapse. Phosphoinositide-dependent kinase 1 (PDK1) is a critical regulator of the PI3K/Akt pathway and has been shown to be frequently activated in leukemia. However, the role of PDK1 in the regulation of LSCs in AML is still not clear. Using a PDK1 conditional deletion MLL-AF9 murine AML model, we revealed that the deletion of PDK1 prolonged the survival of AML mice by inducing LSC apoptosis. This was accompanied by the increased expression of the pro-apoptotic genes Bax and p53 and the reduced expression of Stat5, which has been shown to be constitutively activated in leukemia. Thus, our findings suggest that PDK1 plays an essential role in maintaining LSCs. Further delineating the function of PDK1 in LSCs may provide a new strategy for the improved treatment of AML relapse. PMID:25769952

Hu, Tianyuan; Li, Cong; Zhang, Yingchi; Wang, Le; Peng, Luyun; Cheng, Hui; Wang, Weili; Chu, Yajing; Xu, Mingjiang; Cheng, Tao; Yuan, Weiping

2015-04-17

207

Leukemia mortality by cell type in petroleum workers with potential exposure to benzene  

SciTech Connect

Workers in the petroleum industry are potentially exposed to a variety of petrochemicals, including benzene or benzene-containing liquids. Although a large number of studies of petroleum workers have been conducted to examine leukemia and other cancer risks, few existing studies have investigated cell-type-specific leukemias. One of the major reasons for the lack of cell-type-specific analysis was the small number of deaths by cell type in individual studies. In the present investigation, all cohort studies of petroleum workers in the United States and the United Kingdom were combined into a single database for cell-type-specific leukemia analysis. The majority of these workers were petroleum refinery employees, but production, pipeline, and distribution workers in the petroleum industry were also included. The combined cohort consisted of more than 208,000 petroleum workers, who contributed more than 4.6 million person-years of observation. Based on a meta-analysis of the combined data, cell-type-specific leukemia risks were expressed in terms of standardized mortality ratios (meta-SMRs). The meta-SMR for acute myeloid leukemia was 0.96. The lack of an increase of acute myeloid leukemia was attributed to the low levels of benzene exposure in the petroleum industry, particularly in comparison to benzene exposure levels in some previous studies of workers in other industries, who had been found to experience an increased risk of acute myeloid leukemia. Similarly, no increase in chronic myeloid, acute lymphocytic, or chronic lymphocytic leukemias was found in petroleum workers (meta-SMRs of 0.89, 1.16, and 0.84, respectively). Stratified meta-analyses restricted to refinery studies or to studies with at least 15 years of follow-up yielded similar results. The findings are consistent with those from several recent case-control studies of cell-type-specific leukemia. 95 refs., 4 figs., 10 tabs.

Raabe, G.K. [Mobil Oil Corp., New Hope, PA (United States); Wong, O. [Applied Health Sciences, Inc., San Mateo, CA (United States)

1996-12-01

208

Tartrate-resistant Acid Phosphatase (Acp 5): Identification in Diverse Human Tissues and Dendritic Cells  

Microsoft Academic Search

SUMMARY Histochemical demonstration of tartrate-resistant acid phosphatase (TRAP) is used for the specific identification of osteoclasts. The enzyme, which we have shown to be critical for normal bone development in mice, is also characteristic of monohistiocytes, in- cluding alveolar macrophages, and is associated with diverse pathological conditions such as Gaucher's disease and hairy cell leukemia. TRAP activity is enhanced in

Alison R. Hayman; Paul Macary; Paul J. Lehner; Timothy M. Cox

2001-01-01

209

Cell surface phenotype and in vitro function of adult T-cell leukemia cells.  

PubMed

The cell surface phenotypes of leukemic cells obtained from 30 patients with adult T-cell leukemia (ATL) were examined by means of a panel of OKT monoclonal antibodies and an anti-Tac monoclonal antibody. These leukemic cells were reactive with OKT1, OKT3, OKT4, OKT10, and OKT11 but not with OKT5, OKT6, OKT8 antibodies, suggesting that they were derived from peripheral mature cells included in the OKT4+ "helper/inducer" T-cell subset. Functionally, leukemic cells from none of the nine patients studied stimulated pokeweed mitogen (PWM)-driven immunoglobulin (Ig) synthesis by normal B cells. Suppressor cell activity, however, was found in 17 of 25 patients in PWM-induced Ig production. Fresh or cultured ATL cells from 22 of 23 patients tested expressed Tac antigen (interleukin-2 receptor) on the cell surface. The significance of Tac antigen on ATL cells is discussed in relation to the abnormal regulation of Tac antigen and leukemogenesis. PMID:6094084

Uchiyama, T; Hattori, T; Wano, Y; Tsudo, M; Takatsuki, K; Uchino, H

1983-01-01

210

Fludarabine Phosphate, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma  

ClinicalTrials.gov

B-cell Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma; T-cell Large Granular Lymphocyte Leukemia

2014-12-15

211

CD99 ligation upregulates HSP70 on acute lymphoblastic leukemia cells and concomitantly increases NK cytotoxicity  

PubMed Central

CD99 is present in many human cell types, including high-level surface expression on pediatric B and T leukemias and Ewing tumors (ETs). On B lymphocytes and respective malignancies, its level decreases with the stage of maturation. Inter-individual variability of CD99 on B-cell precursor acute lymphoblastic leukemia (BCP-ALL) blasts was shown recently to be associated with distinct cytogenetic backgrounds. However, CD99 targets remain mainly unknown. Here, we show that administration of an anti-CD99 antibody to B- and T-leukemia cell lines induces heat shock protein 70 (HSP70), both on the cell surface and in the cytoplasm. Investigation of primary BCP-ALL cells rendered similar results. Intriguingly, CD99-induced modulation of HSP70 on ET cells had profiles different from that on leukemia cells. Since HSP70 expression on tumor cells is a prerequisite for natural killer (NK) cell-mediated tumor lysis, we hypothesized that CD99-induced HSP70 may allow targeting of some CD99-positive malignancies via NK-cell cytotoxicity. Our experiments with NK92 cell line demonstrated that leukemia cells with upregulated HSP70 can be successfully killed by effector cells. We consider our data as a new view of CD99 functions and as a basis for the development of a potential anti-tumor strategy based on heat-shock protein activation via CD99 triggering. PMID:23152061

Husak, Z; Dworzak, M N

2012-01-01

212

Cytokine-induced killer cells: A novel immunotherapy strategy for leukemia  

PubMed Central

Cytokine-induced killer (CIK) cells are NK-like T cells derived from peripheral blood mononuclear cells that are co-stimulated and expanded using cytokines for 14–21 days in vitro. CIK cells are a heterogeneous subset of highly-efficient cytotoxic T effector cells that mediate major histocompatibility complex-unrestricted cytotoxicity against a broad array of tumor cells. These effector cells are generated from patients with leukemia or healthy donors who demonstrate similar cytotoxic activity against leukemia blasts. Allogeneic CIK cells retain the ability to produce the graft versus tumor response and generate minimal graft versus host disease. In addition, CIK cells possess no cytotoxicity against normal hematopoietic stem cells in vivo. Leukemia recurrence remains a formidable obstacle, but adoptive immunotherapy offers promise for the eradication of minimal residual disease and prevention of leukemia relapse following hematopoietic stem cell transplantation. CIK cell infusion started a novel generation of adoptive immunotherapy and exhibits particular potential applications in the area of hematological malignancy. In the present study, the previous strategies of leukemia immunotherapy using CIK cells are reviewed and the future directions of development are discussed. PMID:25621022

YANG, XIN-YU; ZENG, HUI; CHEN, FANG-PING

2015-01-01

213

Extremal hairy black holes  

NASA Astrophysics Data System (ADS)

We consider a gravitating system consisting of a scalar field minimally coupled to gravity with a self-interacting potential and an U(1) electromagnetic field. Solving the coupled Einstein-Maxwell-scalar system we find exact hairy charged black hole solutions with the scalar field regular everywhere. We go to the zero temperature limit and we study the effect of the scalar field on the near horizon geometry of an extremal black hole. We find that except a critical value of the charge of the black hole there is also a critical value of the charge of the scalar field beyond of which the extremal black hole is destabilized. We study the thermodynamics of these solutions and we find that if the space is flat then the Reissner-Nordström black hole is thermodynamically preferred, while if the space is AdS the hairy charged black hole is thermodynamically preferred at low temperature.

González, P. A.; Papantonopoulos, Eleftherios; Saavedra, Joel; Vásquez, Yerko

2014-11-01

214

Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity  

Microsoft Academic Search

Emerging evidence suggests cancer stem cells sustain neoplasms; however, little is understood of the normal cell initially targeted and the resultant cancer stem cells. We show here, by tracking individual human leukemia stem cells (LSCs) in nonobese diabetic–severe combined immunodeficiency mice serially transplanted with acute myeloid leukemia cells, that LSCs are not functionally homogeneous but, like the normal hematopoietic stem

Kristin J Hope; Liqing Jin; John E Dick

2004-01-01

215

Free radical production and labile iron pool decrease triggered by subtoxic concentration of aclarubicin in human leukemia cell lines  

E-print Network

of aclarubicin in human leukemia cell lines Doriane Richard, Hamid Morjani, Benoît Chénais* Unité MéDIAN, CNRS manuscript, published in "Leukemia Research 26, 10 (2002) 927-31" #12;2 Abstract Aclarubicin (ACLA), which agent for a broad range of human solid tumors and leukemia. By using dihydroethidium as a fluorescent

Boyer, Edmond

216

A COMPARISON OF THE BOVINE LEUKEMIA AND BOVINE SYNCYTIAL VIRUS STATUS IN UTERO-TUBAL CELLS RECOVERED FROM FLUIDS USED  

E-print Network

A COMPARISON OF THE BOVINE LEUKEMIA AND BOVINE SYNCYTIAL VIRUS STATUS IN UTERO-TUBAL CELLS) (Samagh et al 1977, Serological diagno- sis of bovine leukemia virus infection using dual (glycoprotein, Rotterdam, Aug 29ih-30th ; pp 69-77) that both bovine leukemia virus (BLV) and bovine syncytial virus (BSV

Paris-Sud XI, Université de

217

Cytopathic feline leukemia viruses cause apoptosis in hemolymphatic cells.  

PubMed

Certain isolates of the oncoretrovirus feline leukemia virus (FeLV) are strongly cytopathic for hemolymphatic cells. A major cytopathicity determinant is encoded by the SU envelope glucoprotein gp70. Isolates with subgroup C SU gp70 genes specifically induce apoptosis in hemolymphatic cells but not fibroblasts. In vitro exposure of feline T-cells to FeLV-C leads first to productive viral replication, next to virus-induced cell agglutination, and lastly to apogenesis. This in vitro phenomenon may explain the severe progressive thymic atrophy and erythroid aplasia which follow viremic FeLV-C infection in vivo. Inappropriate apoptosis induction has also been hypothesized to explain the severe thymico-lymphoid atrophy and progressive immune deterioration associated with isolates of FeLV containing variant envelope genes. The influence of envelope hypervariability (variable regions 1 [Vr1] and 5 [Vr5] on virus tropism, viremia induction, neutralizing antibody development and cytopathicity is discussed. Certain potentially cytopathic elements in FeLV SU gp70 Vr5 may derive from replication-defective, poorly expressed, endogenous FeLVs. Other more highly conserved regions in FeLV TM envelope p15E may also influence apoptosis induction. PMID:8822790

Rojko, J L; Hartke, J R; Cheney, C M; Phipps, A J; Neil, J C

1996-01-01

218

City of Hope study identifies potential therapy targeting leukemia stem cells  

Cancer.gov

New research takes aim at stubborn cancer stem cells that are thought to be responsible for treatment resistance and relapse. The study, published by Cell Press in the February 14 issue of the journal Cancer Cell, provides insight into mechanisms associated with the survival of leukemia stem cells and identifies a potential therapeutic target that is specific for these dangerously persistent cells.

219

Blood kinetics, tissue distribution, and radioimaging of anti-common chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody CLL2 in mice transplanted with cCLLa-bearing human leukemia cells  

SciTech Connect

The blood kinetics and biodistribution of anti-common chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody (MoAb) CLL2 were assessed in mice bearing cCLLa+ tumors. The cCLLa is a 69-Kd glycoprotein antigen expressed selectively by malignant B cells in human CLL, hairy cell leukemia (HCL), and prolymphocytic leukemia. Immunoreactive 125I-CLL2 (5 micrograms/mouse, specific activity 4.3 microCi/micrograms) was injected intravenously in mice bearing HCL-derived EH xenografts, and blood kinetics and biodistribution were ascertained up to 16 days postinjection. Radioimages were also obtained up to 72 hours after injecting 10 micrograms/mouse (specific activity 50.1 microCi/micrograms) of 125I-CLL2. Distinct 125I-CLL2 blood kinetics were observed in EH engrafted compared with tumor-free mice including: a longer 125I-CLL2 T 1/2 (153 hours v 72 hours), and a considerably greater blood clearance (173 mg/h v 54.7 mg/h) with biexponential rather than monoexponential configuration; and a greater volume of antibody distribution (31,483 mg v 5,729 mg). These data suggest more rapid tissue uptake by grafted tumours. Preferential 125I-CLL2 uptake by EH tumours relative to normal tissues was observed beginning 24 hours postinjection (mean ratio, 4.2) with average peak tumor 125I-CLL2 levels of 428.7 pg/mg. 125I-CLL2 uptake selectivity by EH tumor cells was also supported by: (1) negligible 125I-CLL2 uptake by cCLLa- Molt-4 xenografts (average 29.1 pg/mg 24 hours postinjection); (2) background uptake of cCLLa-irrelevant MoAb 131I-LEU1 by CD5- EH xenografts (average 31.4 pg/mg 48 hours postinjection); and (3) by scintigraphy. The EH xenograft mouse model might be useful to ascertain preclinically the anti-tumor effect of anti-cCLLa MoAbs and of their conjugated derivatives.

Faguet, G.B.; Agee, J.F.; DiPiro, J.T. (Veterans Administration Medical Center, Augusta, GA (USA))

1990-05-01

220

Crown Gall Disease and Hairy Root Disease 1  

PubMed Central

The neoplastic diseases crown gall and hairy root are incited by the phytopathogenic bacteria Agrobacterium tumefaciens and Agrobacterium rhizogenes, respectively. Although the molecular mechanism of T-DNA transfer to the plant most likely is the same for both species, the physiological basis of tumorigenesis is fundamentally different. Crown gall tumors result from the over-production of the phytohormones auxin and cytokinin specified by A. tumefaciens T-DNA genes. Although the T-DNA of some Riplasmids of A. rhizogenes contains auxin biosynthetic genes, these loci are not always necessary for hairy root formation. Recent experiments suggest that hairy root tumors result from the increased sensitivity of transformed cells to endogenous auxin levels. An understanding of hairy root tumorigenesis will likely result in an increased knowledge of plant developmental processes. Images Figure 1 PMID:16667272

Gelvin, Stanton B.

1990-01-01

221

Adult T-Cell Leukemia: A Review of Epidemiological Evidence  

PubMed Central

Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type I (HTLV-1) infection and often occurs in HTLV-1-endemic areas, such as southwestern Japan, the Caribbean islands, Central and South America, Intertropical Africa, and Middle East. To date, many epidemiological studies have been conducted to investigate the incidence of ATL among general population or HTLV-1 carriers and to identify a variety of laboratory, molecular, and host-specific markers to be possible predictive factors for developing ATL because HTLV-1 infection alone is not sufficient to develop ATL. This literature review focuses on the epidemiology of ATL and the risk factors for the development of ATL from HTLV-1 carriers, while keeping information on the epidemiology of HTLV-1 to a minimum. The main lines of epidemiological evidence are: (1) ATL occurs mostly in adults, at least 20–30?years after the HTLV-1 infection, (2) age at onset differs across geographic areas: the average age in the Central and South America (around 40?years old) is younger than that in Japan (around 60?years old), (3) ATL occurs in those infected in childhood, but seldom occurs in those infected in adulthood, (4) male carriers have about a three- to fivefold higher risk of developing ATL than female, (5) the estimated lifetime risk of developing ATL in HTLV-1 carriers is 6–7% for men and 2–3% for women in Japan, (6) a low anti-Tax reactivity, a high soluble interleukin-2 receptor level, a high anti-HTLV-1 titer, and high levels of circulating abnormal lymphocytes and white blood cell count are accepted risk factors for the development of ATL, and (7) a higher proviral load (more than 4 copies/100 peripheral blood mononuclear cells) is an independent risk factor for progression of ATL. Nevertheless, the current epidemiological evidence is insufficient to fully understand the oncogenesis of ATL. Further well-designed epidemiological studies are needed. PMID:22973265

Iwanaga, Masako; Watanabe, Toshiki; Yamaguchi, Kazunari

2012-01-01

222

[The mechanism of alteronol inhibiting the proliferation of human promyelocytic leukemia HL-60 cells].  

PubMed

This study is to investigate the mechanism of human promyelocytic leukemia HL-60 cells proliferation induced by alteronol in vitro. Human promyelocytic leukemia HL-60 cells cultured in vitro were treated with different concentrations of alteronol. Inhibition rate was detected by SRB assay. Cellular morphological changes were observed by Hoechst and AO/EB (acridine orange/ethidium bromide dye) staining. The apoptosis rate was determined by Annexin V-FITC/PI assay. Cell cycle distribution was determined by flow cytometry. Western blotting analysis was carried out to determine the cell cycle related proteins. The proliferation of HL-60 cells treated with alteronol was inhibited in a concentration-dependent manner. Based on cell viability assay, observation on cell morphology and apoptosis rate, it confirmed that alteronol played an obvious role in proliferation inhibition of human promyelocytic leukemia HL-60 cells, but it did not induce apoptosis in human promyelocytic leukemia HL-60 cells in different concentrations groups. Alteronol could effectively inhibit the proliferation of human promyelocytic leukemia HL-60 cells inducing cell cycle arrest at G1 phase, as well as, alteration expression of cell cycle proteins level of CyclinD1 and pRb. PMID:23387080

Liu, Liang-Liang; Chen, Na; Yuan, Xuan; Yao, Ying; Zhang, Bo; Zheng, Qiu-Sheng

2012-11-01

223

Critical molecular pathways in cancer stem cells of chronic myeloid leukemia  

Microsoft Academic Search

Inhibition of BCR-ABL with kinase inhibitors in the treatment of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) is highly effective in controlling but not curing the disease. This is largely due to the inability of these kinase inhibitors to kill leukemia stem cells (LSCs) responsible for disease relapse. This stem cell resistance is not associated with the BCR-ABL kinase domain mutations

Y Chen; C Peng; C Sullivan; D Li; S Li

2010-01-01

224

Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia  

ClinicalTrials.gov

Leukemias; Acute Myeloid Leukemia (AML); Acute Lymphocytic Leukemia (ALL); Adult T Cell Leukemia (ATL); Chronic Myeloid Leukemia (CML-BP); Chronic Lymphocytic Leukemia (CLL); Myelodysplastic Syndrome (MDS); Chronic Myelomonocytic Leukemia (CMML)

2009-01-29

225

Musashi2 sustains the mixed-lineage leukemia-driven stem cell regulatory program.  

PubMed

Leukemia stem cells (LSCs) are found in most aggressive myeloid diseases and contribute to therapeutic resistance. Leukemia cells exhibit a dysregulated developmental program as the result of genetic and epigenetic alterations. Overexpression of the RNA-binding protein Musashi2 (MSI2) has been previously shown to predict poor survival in leukemia. Here, we demonstrated that conditional deletion of Msi2 in the hematopoietic compartment results in delayed leukemogenesis, reduced disease burden, and a loss of LSC function in a murine leukemia model. Gene expression profiling of these Msi2-deficient animals revealed a loss of the hematopoietic/leukemic stem cell self-renewal program and an increase in the differentiation program. In acute myeloid leukemia patients, the presence of a gene signature that was similar to that observed in Msi2-deficent murine LSCs correlated with improved survival. We determined that MSI2 directly maintains the mixed-lineage leukemia (MLL) self-renewal program by interacting with and retaining efficient translation of Hoxa9, Myc, and Ikzf2 mRNAs. Moreover, depletion of MLL target Ikzf2 in LSCs reduced colony formation, decreased proliferation, and increased apoptosis. Our data provide evidence that MSI2 controls efficient translation of the oncogenic LSC self-renewal program and suggest MSI2 as a potential therapeutic target for myeloid leukemia. PMID:25664853

Park, Sun-Mi; Gönen, Mithat; Vu, Ly; Minuesa, Gerard; Tivnan, Patrick; Barlowe, Trevor S; Taggart, James; Lu, Yuheng; Deering, Raquel P; Hacohen, Nir; Figueroa, Maria E; Paietta, Elisabeth; Fernandez, Hugo F; Tallman, Martin S; Melnick, Ari; Levine, Ross; Leslie, Christina; Lengner, Christopher J; Kharas, Michael G

2015-03-01

226

Gene expression profiling in T-cell acute lymphoblastic leukemia.  

PubMed

T-cell acute lymphoblastic leukemia (T-ALL) presents a difficult medical problem. T-ALL's clinical features and the biological properties of the leukemia cells are not predictive of prognosis, and thus have not been useful for risk-specific adjustments in therapeutic intensity. Microarray gene expression analyses of T-cell leukemic lymphoblasts have not only improved our understanding of the biological heterogeneity of this disease but have revealed clinically relevant molecular subtypes. Five different multistep molecular pathways have been identified that lead to T-ALL, involving activation of different T-ALL oncogenes: (1) HOX11, (2) HOX11L2, (3) TAL1 plus LMO1/2, (4) LYL1 plus LMO2, and (5) MLL-ENL. Gene expression studies indicate activation of a subset of these genes-HOX11, TAL1, LYL1, LMO1, and LMO2-in a much larger fraction of T-ALL cases than those harboring activating chromosomal translocations. In many such cases, the abnormal expression of one or more of these oncogenes is biallelic, implicating upstream regulatory mechanisms. Among these molecular subtypes, overexpression of the HOX11 orphan homeobox gene occurs in approximately 5% to 10% of childhood and 30% of adult T-ALL cases. Patients with HOX11-positive lymphoblasts have an excellent prognosis when treated with modern combination chemotherapy, while cases at high risk of early failure are included largely in the TAL1- and LYL1-positive groups. Supervised learning approaches applied to microarray data have identified a group of genes whose expression is able to distinguish high-risk cases. Further analyses of gene expression signatures of T-ALL lymphoblasts are especially needed for patients treated on modern combination chemotherapy trials to clearly distinguish the 10% to 15% of patients who fail induction or relapse in the first year of treatment. These high-risk patients would be ideal candidates for more intensive therapies in first remission, such as myeloablative regimens with stem cell rescue. Based on the rapid pace of research in T-ALL, made possible in large part through microarray technology, deep analysis of molecular pathways should lead to new and much more specific targeted therapies. PMID:14582078

Ferrando, Adolfo A; Look, A Thomas

2003-10-01

227

Chronic Lymphocytic Leukemia  

MedlinePLUS

Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

228

Chronic Myeloid Leukemia  

MedlinePLUS

Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

229

IGF binding protein 2 is a cell-autonomous factor supporting survival and migration of acute leukemia cells  

PubMed Central

Background The role of IGF binding protein 2 (IGFBP2) in cancer development is intriguing. Previously we identified IGFBP2 as an extrinsic factor that supports the activity of hematopoietic stem cells (HSCs). Methods and results Here we investigated the role of IGFBP2 in in human leukemia cells and in the retroviral AML1-ETO9a transplantation acute myeloid leukemia (AML) mouse model. Results IGFBP2 is highly expressed in certain human AML and acute lymphoblastic leukemia (ALL) cells. Inhibition of expression of endogenous IGFBP2 in human leukemia cells led to elevated apoptosis and decreased migration and, consistently, to decreased activation of AKT and other signaling molecules. We also studied the effects of IGFBP2 knockout in the retroviral AML1-ETO9a transplantation AML mouse model. The deletion of IGFBP2 in donor AML cells significantly decreased leukemia development in transplanted mice. Lack of IGFBP2 resulted in upregulation of PTEN expression and downregulation of AKT activation, in the mouse AML cells. The treatment of IGFBP2 deficient AML cells with a PTEN inhibitor restored the wild-type colony forming ability. The deletion of IGFBP2 also led to decreased AML infiltration into peripheral organs and tissues, suggesting that IGFBP2 is required for the migration of AML cells out of bone marrow. Conclusion IGFBP2 is a critical cell-autonomous factor that promotes the survival and migration of acute leukemia cells. PMID:24191913

2013-01-01

230

Kinase-Independent Mechanisms of Resistance of Leukemia Stem Cells to Tyrosine Kinase Inhibitors  

PubMed Central

Summary Tyrosine kinase inhibitors such as imatinib mesylate have changed the clinical course of chronic myeloid leukemia; however, the observation that these inhibitors do not target the leukemia stem cell implies that patients need to maintain lifelong therapy. The mechanism of this phenomenon is unclear: the question of whether tyrosine kinase inhibitors are inactive inside leukemia stem cells or whether leukemia stem cells do not require breakpoint cluster region (Bcr)-Abl signaling is currently under debate. Herein, I propose an alternative model: perhaps the leukemia stem cell requires Bcr-Abl, but is dependent on its kinase-independent functions. Kinases such as epidermal growth factor receptor and Janus kinase 2 possess kinase-independent roles in regulation of gene expression; it is worth investigating whether Bcr-Abl has similar functions. Mechanistically, Bcr-Abl is able to activate the Ras, phosphatidylinositol 3-kinase/Akt, and/or the Src-kinase Hck/Stat5 pathways in a scaffolding-dependent manner. Whereas the scaffolding activity of Bcr-Abl with Grb2 is dependent on autophosphorylation, kinases such as Hck can use Bcr-Abl as substrate, inducing phosphorylation of Y177 to enable scaffolding ability in the absence of Bcr-Abl catalytic activity. It is worth investigating whether leukemia stem cells exclusively express kinases that are able to use Bcr-Abl as substrate. A kinase-independent role for Bcr-Abl in leukemia stem cells would imply that drugs that target Bcr-Abl’s scaffolding ability or its DNA-binding ability should be used in conjunction with current therapeutic regimens to increase their efficacy and eradicate the stem cells of chronic myeloid leukemia PMID:24598782

2014-01-01

231

Kinase-independent mechanisms of resistance of leukemia stem cells to tyrosine kinase inhibitors.  

PubMed

Tyrosine kinase inhibitors such as imatinib mesylate have changed the clinical course of chronic myeloid leukemia; however, the observation that these inhibitors do not target the leukemia stem cell implies that patients need to maintain lifelong therapy. The mechanism of this phenomenon is unclear: the question of whether tyrosine kinase inhibitors are inactive inside leukemia stem cells or whether leukemia stem cells do not require breakpoint cluster region (Bcr)-Abl signaling is currently under debate. Herein, I propose an alternative model: perhaps the leukemia stem cell requires Bcr-Abl, but is dependent on its kinase-independent functions. Kinases such as epidermal growth factor receptor and Janus kinase 2 possess kinase-independent roles in regulation of gene expression; it is worth investigating whether Bcr-Abl has similar functions. Mechanistically, Bcr-Abl is able to activate the Ras, phosphatidylinositol 3-kinase/Akt, and/or the Src-kinase Hck/Stat5 pathways in a scaffolding-dependent manner. Whereas the scaffolding activity of Bcr-Abl with Grb2 is dependent on autophosphorylation, kinases such as Hck can use Bcr-Abl as substrate, inducing phosphorylation of Y177 to enable scaffolding ability in the absence of Bcr-Abl catalytic activity. It is worth investigating whether leukemia stem cells exclusively express kinases that are able to use Bcr-Abl as substrate. A kinase-independent role for Bcr-Abl in leukemia stem cells would imply that drugs that target Bcr-Abl's scaffolding ability or its DNA-binding ability should be used in conjunction with current therapeutic regimens to increase their efficacy and eradicate the stem cells of chronic myeloid leukemia. PMID:24598782

Ichim, Christine Victoria

2014-04-01

232

The cytotoxic effect of 2-acylated-1,4-naphthohydroquinones on leukemia/lymphoma cells  

PubMed Central

Here, we tested seven 2-acylated-1,4-hydronaphthoquinones for their cytotoxic effects on a panel of cancer lymphoma/leukemia cells and compared to a non-cancer origin cell line. Several naphthohydroquinones exhibited selective cytotoxic effects on lymphoma/leukemia cells with lowest activity on non-cancer cells. The mode of cell death induced by an acylated naphthohydroquinone, which has a long alkyl chain, was found to be via apoptosis. Furthermore, the naphthohydroquinone provoked mitochondria depolarization and activation of its downstream effector, caspase-3, thus implicating the intrinsic apoptotic pathway as its mechanism to exert cell death. PMID:24368029

Pedroza, Diego A.; De Leon, Fernando; Varela-Ramirez, Armando; Lema, Carolina; Aguilera, Renato J.; Mito, Shizue

2014-01-01

233

Nanoarchitectured electrochemical cytosensors for selective detection of leukemia cells and quantitative evaluation of death receptor expression on cell surfaces.  

PubMed

The variable susceptibility to the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment observed in various types of leukemia cells is related to the difference in the expression levels of death receptors, DR4 and DR5, on the cell surfaces. Quantifying the DR4/DR5 expression status on leukemia cell surfaces is of vital importance to the development of diagnostic tools to guide death receptor-based leukemia treatment. Taking the full advantages of novel nanobiotechnology, we have developed a robust electrochemical cytosensing approach toward ultrasensitive detection of leukemia cells with detection limit as low as ~40 cells and quantitative evaluation of DR4/DR5 expression on leukemia cell surfaces. The optimization of electron transfer and cell capture processes at specifically tailored nanobiointerfaces and the incorporation of multiple functions into rationally designed nanoprobes provide unique opportunities of integrating high specificity and signal amplification on one electrochemical cytosensor. The high sensitivity and selectivity of this electrochemical cytosensing approach also allows us to evaluate the dynamic alteration of DR4/DR5 expression on the surfaces of living cells in response to drug treatments. Using the TRAIL-resistant HL-60 cells and TRAIL-sensitive Jurkat cells as model cells, we have further verified that the TRAIL susceptibility of various types of leukemia cells is directly correlated to the surface expression levels of DR4/DR5. This versatile electrochemical cytosensing platform is believed to be of great clinical value for the early diagnosis of human leukemia and the evaluation of therapeutic effects on leukemia patients after radiation therapy or drug treatment. PMID:23621478

Zheng, Tingting; Fu, Jia-Ju; Hu, Lihui; Qiu, Fan; Hu, Minjin; Zhu, Jun-Jie; Hua, Zi-Chun; Wang, Hui

2013-06-01

234

Metabolism of arsenic trioxide in acute promyelocytic leukemia cells.  

PubMed

Arsenic trioxide (As2O3) effectively induces complete clinical and molecular remissions in acute promyelocytic leukemia (APL) patients and triggers apoptosis in APL cells. The effect induced by As2O3 is also associated with extensive genomic-wide epigenetic changes with large-scale alterations in DNA methylation. We investigated the As2O3 metabolism in association with factors involved in the production of its methylated metabolites in APL-derived cell line, NB4. We used high performance liquid chromatography (HPLC) technique to detect As2O3 metabolites in NB4 cells. The effects of As2O3 on glutathione level, S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) levels were investigated. Also, we studied the expression levels of arsenic methyltransferase (AS3MT) and DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) by real-time PCR. Our results show that after As2O3 entry into the cell, it was converted into methylated metabolites, mono-methylarsenic (MMA) and dimethylarsenic (DMA). The glutathione (GSH) production was increased in parallel with the methylated metabolites formations. As2O3 treatment inhibited DNMTs (DNMT1, DNMT3a, and DNMT3b) in dose- and time-dependent manners. The SAH levels in As2O3-treated cells were increased; however, the SAM level was not affected. The present study shows that APL cell is capable of metabolizing As2O3. The continuous formation of intracellular methylated metabolites, the inhibition of DNMTs expression levels and the increase of SAH level by As2O3 biotransformation would probably affect the DNMTs-methylated DNA methylation in a manner related to the extent of DNA hypomethylation. Production of intracellular methylated metabolites and epigenetic changes of DNA methylation during As2O3 metabolism may contribute to the therapeutic effect of As2O3 in APL. PMID:24819152

Khaleghian, Ali; Ghaffari, Seyed H; Ahmadian, Shahin; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir

2014-10-01

235

The Notch driven long non-coding RNA repertoire in T-cell acute lymphoblastic leukemia.  

PubMed

Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting a role as an essential driver for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34(+) thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from ex vivo isolated Notch active CD34(+) and Notch inactive CD4(+)CD8(+) thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publicly available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T cells. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way for the development of novel therapeutic strategies that target hyperactive Notch signaling in human T-cell acute lymphoblastic leukemia. PMID:25344525

Durinck, Kaat; Wallaert, Annelynn; Van de Walle, Inge; Van Loocke, Wouter; Volders, Pieter-Jan; Vanhauwaert, Suzanne; Geerdens, Ellen; Benoit, Yves; Van Roy, Nadine; Poppe, Bruce; Soulier, Jean; Cools, Jan; Mestdagh, Pieter; Vandesompele, Jo; Rondou, Pieter; Van Vlierberghe, Pieter; Taghon, Tom; Speleman, Frank

2014-12-01

236

The Notch driven long non-coding RNA repertoire in T-cell acute lymphoblastic leukemia  

PubMed Central

Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting a role as an essential driver for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34+ thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from ex vivo isolated Notch active CD34+ and Notch inactive CD4+CD8+ thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publicly available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T cells. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way for the development of novel therapeutic strategies that target hyperactive Notch signaling in human T-cell acute lymphoblastic leukemia. PMID:25344525

Durinck, Kaat; Wallaert, Annelynn; Van de Walle, Inge; Van Loocke, Wouter; Volders, Pieter-Jan; Vanhauwaert, Suzanne; Geerdens, Ellen; Benoit, Yves; Van Roy, Nadine; Poppe, Bruce; Soulier, Jean; Cools, Jan; Mestdagh, Pieter; Vandesompele, Jo; Rondou, Pieter; Van Vlierberghe, Pieter; Taghon, Tom; Speleman, Frank

2014-01-01

237

Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia.  

PubMed

To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC(1280) library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 ?M drug concentration. Only one of these compounds, quinacrine, showed low activity in normal PBMCs and was therefore selected for further preclinical evaluation. Mining the NCI-60 and the NextBio databases demonstrated leukemia sensitivity and the ability of quinacrine to reverse myeloid leukemia gene expression. Mechanistic exploration was performed using the NextBio bioinformatic software using gene expression analysis of drug exposed acute myeloid leukemia cultures (HL-60) in the database. Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation. The highest drug-drug correlation was to ellipticine, a known RNA polymerase I inhibitor. These results were validated by additional gene expression analysis performed in-house. Quinacrine induced early inhibition of protein synthesis supporting these predictions. The results suggest that quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis. PMID:25885427

Eriksson, A; Österroos, A; Hassan, S; Gullbo, J; Rickardson, L; Jarvius, M; Nygren, P; Fryknäs, M; Höglund, M; Larsson, R

2015-01-01

238

Emerging Therapeutic Strategies for Targeting Chronic Myeloid Leukemia Stem Cells  

PubMed Central

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder. Current targeted therapies designed to inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein have made a significant breakthrough in the treatment of CML patients. However, CML remains a chronic disease that a patient must manage for life. Although tyrosine kinase inhibitors (TKI) therapy has completely transformed the prognosis of CML, it has made the therapeutic management more complex. The interruption of TKI treatment results in early disease progression because it does not eliminate quiescent CML stem cells which remain a potential reservoir for disease relapse. This highlights the need to develop new therapeutic strategies for CML to achieve a permanent cure, and to allow TKI interruption. This review summarizes recent research done on alternative targeted therapies with a particular focus on some important signaling pathways (such as Alox5, Hedgehog, Wnt/b-catenin, autophagy, and PML) that have the potential to target CML stem cells and potentially provide cure for CML. PMID:23935640

El Sabban, Maya; Mouteirik, Maha; Nasr, Rihab

2013-01-01

239

Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors  

PubMed Central

Three distinct immature T-cell acute lymphoblastic leukemia entities have been described including cases that express an early T-cell precursor immunophenotype or expression profile, immature MEF2C-dysregulated T-cell acute lymphoblastic leukemia cluster cases based on gene expression analysis (immature cluster) and cases that retain non-rearranged TRG@ loci. Early T-cell precursor acute lymphoblastic leukemia cases exclusively overlap with immature cluster samples based on the expression of early T-cell precursor acute lymphoblastic leukemia signature genes, indicating that both are featuring a single disease entity. Patients lacking TRG@ rearrangements represent only 40% of immature cluster cases, but no further evidence was found to suggest that cases with absence of bi-allelic TRG@ deletions reflect a distinct and even more immature disease entity. Immature cluster/early T-cell precursor acute lymphoblastic leukemia cases are strongly enriched for genes expressed in hematopoietic stem cells as well as genes expressed in normal early thymocyte progenitor or double negative-2A T-cell subsets. Identification of early T-cell precursor acute lymphoblastic leukemia cases solely by defined immunophenotypic criteria strongly underestimates the number of cases that have a corresponding gene signature. However, early T-cell precursor acute lymphoblastic leukemia samples correlate best with a CD1 negative, CD4 and CD8 double negative immunophenotype with expression of CD34 and/or myeloid markers CD13 or CD33. Unlike various other studies, immature cluster/early T-cell precursor acute lymphoblastic leukemia patients treated on the COALL-97 protocol did not have an overall inferior outcome, and demonstrated equal sensitivity levels to most conventional therapeutic drugs compared to other pediatric T-cell acute lymphoblastic leukemia patients. PMID:23975177

Zuurbier, Linda; Gutierrez, Alejandro; Mullighan, Charles G.; Canté-Barrett, Kirsten; Gevaert, A. Olivier; de Rooi, Johan; Li, Yunlei; Smits, Willem K.; Buijs-Gladdines, Jessica G.C.A.M.; Sonneveld, Edwin; Look, A. Thomas; Horstmann, Martin; Pieters, Rob; Meijerink, Jules P.P.

2014-01-01

240

Dose-dependent killing of leukemia cells by low-temperature plasma  

NASA Astrophysics Data System (ADS)

The effect of low-temperature atmospheric pressure plasma towards the progression of cancerous human T-cell leukemia cells was investigated. The plasma pencil, which utilizes short duration high voltage pulses, was used to generate a low-temperature plasma (LTP) plume in ambient air. Our data showed that cell morphology and cell viability were affected in a dose-dependent manner after treatment with LTP. The outcome of this study revealed that the effect of plasma exposure was not immediate, but had a delayed effect and increasing the time of plasma exposure resulted in increased leukemia cell death.

Barekzi, N.; Laroussi, M.

2012-10-01

241

Hairy Root Transformation Using Agrobacterium rhizogenes as a Tool for Exploring Cell Type-Specific Gene Expression and Function Using Tomato as a Model1[W][OPEN  

PubMed Central

Agrobacterium rhizogenes (or Rhizobium rhizogenes) is able to transform plant genomes and induce the production of hairy roots. We describe the use of A. rhizogenes in tomato (Solanum spp.) to rapidly assess gene expression and function. Gene expression of reporters is indistinguishable in plants transformed by Agrobacterium tumefaciens as compared with A. rhizogenes. A root cell type- and tissue-specific promoter resource has been generated for domesticated and wild tomato (Solanum lycopersicum and Solanum pennellii, respectively) using these approaches. Imaging of tomato roots using A. rhizogenes coupled with laser scanning confocal microscopy is facilitated by the use of a membrane-tagged protein fused to a red fluorescent protein marker present in binary vectors. Tomato-optimized isolation of nuclei tagged in specific cell types and translating ribosome affinity purification binary vectors were generated and used to monitor associated messenger RNA abundance or chromatin modification. Finally, transcriptional reporters, translational reporters, and clustered regularly interspaced short palindromic repeats-associated nuclease9 genome editing demonstrate that SHORT-ROOT and SCARECROW gene function is conserved between Arabidopsis (Arabidopsis thaliana) and tomato. PMID:24868032

Ron, Mily; Kajala, Kaisa; Pauluzzi, Germain; Wang, Dongxue; Reynoso, Mauricio A.; Zumstein, Kristina; Garcha, Jasmine; Winte, Sonja; Masson, Helen; Inagaki, Soichi; Federici, Fernán; Sinha, Neelima; Deal, Roger B.; Bailey-Serres, Julia; Brady, Siobhan M.

2014-01-01

242

Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia  

PubMed Central

BACKGROUND Relapsed acute lymphoblastic leukemia (ALL) is difficult to treat despite the availability of aggressive therapies. Chimeric antigen receptor–modified T cells targeting CD19 may overcome many limitations of conventional therapies and induce remission in patients with refractory disease. METHODS We infused autologous T cells transduced with a CD19-directed chimeric antigen receptor (CTL019) lentiviral vector in patients with relapsed or refractory ALL at doses of 0.76×106 to 20.6×106 CTL019 cells per kilogram of body weight. Patients were monitored for a response, toxic effects, and the expansion and persistence of circulating CTL019 T cells. RESULTS A total of 30 children and adults received CTL019. Complete remission was achieved in 27 patients (90%), including 2 patients with blinatumomab-refractory disease and 15 who had undergone stem-cell transplantation. CTL019 cells proliferated in vivo and were detectable in the blood, bone marrow, and cerebrospinal fluid of patients who had a response. Sustained remission was achieved with a 6-month event-free survival rate of 67% (95% confidence interval [CI], 51 to 88) and an overall survival rate of 78% (95% CI, 65 to 95). At 6 months, the probability that a patient would have persistence of CTL019 was 68% (95% CI, 50 to 92) and the probability that a patient would have relapse-free B-cell aplasia was 73% (95% CI, 57 to 94). All the patients had the cytokine-release syndrome. Severe cytokine-release syndrome, which developed in 27% of the patients, was associated with a higher disease burden before infusion and was effectively treated with the anti–interleukin-6 receptor antibody tocilizumab. CONCLUSIONS Chimeric antigen receptor–modified T-cell therapy against CD19 was effective in treating relapsed and refractory ALL. CTL019 was associated with a high remission rate, even among patients for whom stem-cell transplantation had failed, and durable remissions up to 24 months were observed. (Funded by Novartis and others; CART19 ClinicalTrials.gov numbers, NCT01626495 and NCT01029366.) PMID:25317870

Maude, Shannon L.; Frey, Noelle; Shaw, Pamela A.; Aplenc, Richard; Barrett, David M.; Bunin, Nancy J.; Chew, Anne; Gonzalez, Vanessa E.; Zheng, Zhaohui; Lacey, Simon F.; Mahnke, Yolanda D.; Melenhorst, Jan J.; Rheingold, Susan R.; Shen, Angela; Teachey, David T.; Levine, Bruce L.; June, Carl H.; Porter, David L.; Grupp, Stephan A.

2014-01-01

243

Histone deacetylase inhibitors (HDI) cause DNA damage in leukemia cells: a mechanism for leukemia-specific HDI-dependent apoptosis?  

PubMed

Histone deacetylase inhibitors (HDI) increase gene expression through induction of histone acetylation. However, it remains unclear whether increases in specific gene expression events determine the apoptotic response following HDI administration. Herein, we show that a variety of HDI trigger in hematopoietic cells not only widespread histone acetylation and DNA damage responses but also actual DNA damage, which is significantly increased in leukemic cells compared with normal cells. Thus, increase in H2AX and ataxia telangiectasia mutated (ATM) phosphorylation, early markers of DNA damage, occurs rapidly following HDI administration. Activation of the DNA damage and repair response following HDI treatment is further emphasized by localizing DNA repair proteins to regions of DNA damage. These events are followed by subsequent apoptosis of neoplastic cells but not normal cells. Our data indicate that induction of apoptosis by HDI may result predominantly through accumulation of excessive DNA damage in leukemia cells, leading to activation of apoptosis. PMID:16877702

Gaymes, Terry J; Padua, Rose Ann; Pla, Marika; Orr, Stephen; Omidvar, Nader; Chomienne, Christine; Mufti, Ghulam J; Rassool, Feyruz V

2006-08-01

244

Role for protein geranylgeranylation in adult T-cell leukemia cell survival  

SciTech Connect

Adult T-cell leukemia (ATL) is a fatal lymphoproliferative disease that develops in human T-cell leukemia virus type I (HTLV-I)-infected individuals. Despite the accumulating knowledge of the molecular biology of HTLV-I-infected cells, effective therapeutic strategies remain to be established. Recent reports showed that the hydroxyl-3-methylglutaryl (HMG)-CoA reductase inhibitor statins have anti-proliferative and apoptotic effects on certain tumor cells through inhibition of protein prenylation. Here, we report that statins hinder the survival of ATL cells and induce apoptotic cell death. Inhibition of protein geranylgeranylation is responsible for these effects, since simultaneous treatment with isoprenoid precursors, geranylgeranyl pyrophosphate or farnesyl pyrophosphate, but not a cholesterol precursor squalene, restored the viability of ATL cells. Simvastatin inhibited geranylgeranylation of small GTPases Rab5B and Rac1 in ATL cells, and a geranylgeranyl transferase inhibitor GGTI-298 reduced ATL cell viability more efficiently than a farnesyl transferase inhibitor FTI-277. These results not only unveil an important role for protein geranylgeranylation in ATL cell survival, but also implicate therapeutic potentials of statins in the treatment of ATL.

Nonaka, Mizuho [Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Bunkyo-ku, Tokyo 113-8510 (Japan); Retrovirus Research Unit, RIKEN, Saitama (Japan); Uota, Shin; Saitoh, Yasunori [Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Bunkyo-ku, Tokyo 113-8510 (Japan); Takahashi, Mayumi [Department of Hematology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo (Japan); Sugimoto, Haruyo; Amet, Tohti [Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Bunkyo-ku, Tokyo 113-8510 (Japan); Arai, Ayako; Miura, Osamu [Department of Hematology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo (Japan); Yamamoto, Naoki [Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Bunkyo-ku, Tokyo 113-8510 (Japan); AIDS Research Center, National Institute of Infectious Diseases, Tokyo (Japan); Yamaoka, Shoji [Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Bunkyo-ku, Tokyo 113-8510 (Japan)], E-mail: shojmmb@tmd.ac.jp

2009-01-15

245

Human T cell leukemia virus type 1 infection drives spontaneous proliferation of natural killer cells  

PubMed Central

Most human T cell leukemia virus type 1 (HTLV-1) infected subjects remain asymptomatic throughout their lives, with a few individuals developing HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T cell leukemia. Lymphocytes from about half of HTLV-1 infected subjects spontaneously proliferate in vitro, and how this phenomenon relates to symptomatic disease outcome and viral burden is poorly understood. Spontaneous proliferation was measured in lymphocyte subsets, and these findings were correlated with HTLV-1 proviral load and Tax expression in peripheral blood mononuclear cells (PBMCs). We found that in addition to previously described vigorous CD8+ T cell spontaneous proliferation, natural killer (NK) cells spontaneously proliferated to a similar high level, resulting in expansion of CD56-expressing NK cells. Spontaneous NK cell proliferation positively correlated with HTLV-1 proviral load but not with Tax expression or the presence of HAM/TSP. The strongest correlate with clinical outcome in this cohort was the ability of cells to express Tax, while HTLV-1 proviral load was more closely related to spontaneous NK cell proliferation. These results demonstrate that spontaneous proliferation, Tax expression, and proviral load are inter-related but not equivalent, and that spontaneous lymphocyte proliferation is not restricted to T cells, the targets of HTLV-1 infection. PMID:20640055

Hirschkorn, Dale F; DeVita, Deborah A; Lee, Tzong-Hae; Murphy, Eedward L

2010-01-01

246

Interleukin-2 receptor (Tac antigen) expressed on adult T cell leukemia cells.  

PubMed

We studied the expression of the interleukin-2 (IL-2) receptor and the proliferative response to exogenous IL-2 of peripheral blood leukemic cells from patients with adult T cell leukemia (ATL) in order to see whether IL-2 receptor expressed on ATL cells is different from normal IL-2 receptor and whether it plays a role in the neoplastic growth in ATL. Peripheral blood leukemic cells from 42 patients with ATL examined expressed IL-2 receptors that were detected by anti-Tac monoclonal antibody when examined immediately after the separation of cells or after the culture for 24 or 48 h. The number of anti-Tac binding sites ranged from 3,100 to 11,400 in fresh cells and from 3,600 to 96,000/cell in short-term cultured leukemic cells, whereas phytohemagglutinin-P (PHA-P)-stimulated normal T cells exhibited 6,900-35,000 anti-Tac binding sites per cell. ATL-derived and human T cell leukemia/lymphoma virus, type I (HTLV-I)-infected cell lines such as MT-1 and Hut102 expressed a much higher number of anti-Tac binding sites. Leukemic cells from 15 patients with ATL examined showed no or very poor proliferative response to various concentrations of immunoaffinity-purified IL-2, although they expressed Tac antigen (Ag). Radiolabeled IL-2 binding experiments demonstrated that ATL leukemic cells could bind IL-2, and they expressed both high and low affinity IL-2 receptors, although the number of high affinity IL-2 receptor was much less than that of low affinity IL-2 receptor and that of anti-Tac binding sites. In contrast, leukemic T cells from a patient with T cell chronic lymphocytic leukemia (CLL), in whom HTLV-I infection was not demonstrated, responded as well as PHA-P-stimulated normal T cells, and their IL-2 receptors, unlike ATL cells, were modulated (down regulated) by anti-Tac antibody. No differences were noted between ATL cells and normal activated T cells in one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of the IL-2 receptor. Thus, leukemic cells in ATL spontaneously and continuously express IL-2 receptor, which appears to be abnormally regulated and unresponsive to IL-2. These results, taken together with those on normal IL-2 receptors on HTLV-I-negative T-CLL cells, suggest that abnormal expression of the IL-2 receptor in ATL is closely associated with HTLV-I infection and may play a role in the neoplastic growth of ATL cells. PMID:2993359

Uchiyama, T; Hori, T; Tsudo, M; Wano, Y; Umadome, H; Tamori, S; Yodoi, J; Maeda, M; Sawami, H; Uchino, H

1985-08-01

247

Inhibition of activated STAT5 in Bcr/Abl expressing leukemia cells with new pimozide derivatives.  

PubMed

STATs are transcription factors acting as intracellular signaling after stimulation with cytokines, growth factors and hormones. STAT5 is also constitutively active in many forms of cancers, including chronic myelogenous leukemia, acute lymphoblastic leukemia and Hodgkin's lymphoma. Recently, literature reported that the neuroleptic drug pimozide inhibits STAT5 phosphorylation inducing apoptosis in CML cells. We undertook an investigation from pimozide structure, obtaining simple derivatives with cytotoxic and STAT5-inhibitory activity, two of them markedly more potent than pimozide. PMID:25131537

Rondanin, Riccardo; Simoni, Daniele; Romagnoli, Romeo; Baruchello, Riccardo; Marchetti, Paolo; Costantini, Cristiana; Fochi, Sara; Padroni, Giacomo; Grimaudo, Stefania; Pipitone, Rosaria Maria; Meli, Maria; Tolomeo, Manlio

2014-09-15

248

Small-molecule inhibitor which reactivates p53 in human T-cell leukemia virus type 1-transformed cells  

Microsoft Academic Search

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of the aggressive and fatal disease adult T-cell leukemia. Previous studies have demonstrated that the HTLV-1-encoded Tax protein inhibits the function of tumor suppressor p53 through a Tax-induced NF-kappaB pathway. Given these attributes, we were interested in the activity of small-molecule inhibitor 9-aminoacridine (9AA), an anticancer drug that targets

Kyung-Jin Jung; Arindam Dasgupta; Keven Huang; Soo-Jin Jeong; Cynthia Ann Pise-Masison; Katerina V. Gurova; John N. Brady

2008-01-01

249

Interleukin 10 Induces Apoptotic Cell Death of B-Chronic Lymphocytic Leukemia Cells  

Microsoft Academic Search

Summary Recent studies have established that interleukin (IL)-10 induces growth and most notably differentiation of normal human B lymphocytes. We studied here the effects of IL-10 on the proliferation and survival of B-chronic lymphocytic leukemia (B-CLL) cells. IL-10 was found to inhibit 54-96% of the spontaneous tritiated thymidine incorporation observed in 3 of 12 B-CLL samples. Furthermore, IL-10 decreased the

Anne-Catherine Fluckiger; Isabelle Durand; Jacques Banchereau

250

HDAC1 and Klf4 interplay critically regulates human myeloid leukemia cell proliferation  

PubMed Central

Acute myeloid leukemia (AML) is recognized as a complex disease of hematopoietic stem cell disorders, but its pathogenesis mechanisms, diagnosis, and treatment remain unclear. General histone deacetylase (HDAC) inhibitors have been used in blood cancers including AML, but the lack of gene specificity greatly limits their anti-cancer effects and clinical applications. Here, we found that HDAC1 expression was negatively correlated with that of Krüppel-like factor 4 (Klf4) and that AML patients with lower HDAC1 level had better prognosis. Further, knockdown of HDAC1 in leukemia cells K562, HL-60, and U937 significantly increased Klf4 expression and inhibited cell cycle progression and cell proliferation, similar results were found for HDAC inhibitors (VPA and mocetinostat). Moreover, overexpression or knockdown of Klf4 could markedly block the effects of HDAC1 overexpression or knockdown on leukemia cells in vitro and in vivo, respectively. Mechanistic analyses demonstrated that HDAC1 and Klf4 competitively bound to the promoter region of Klf4 and oppositely regulated Klf4 expression in myeloid leukemia. We identified HDAC1 as a potential specific target for repressing cell proliferation and inducing cell cycle arrest through interplay and modulation of Klf4 expression, suggests that HDAC1 and Klf4 are potential new molecular markers and targets for clinical diagnosis, prognosis, and treatment of myeloid leukemia. PMID:25341045

Huang, Y; Chen, J; Lu, C; Han, J; Wang, G; Song, C; Zhu, S; Wang, C; Li, G; Kang, J; Wang, J

2014-01-01

251

Acute Myeloid Leukemia  

MedlinePLUS

Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

252

Adult T-cell leukemia/lymphoma with EBV-positive Hodgkin-like cells  

PubMed Central

SUMMARY Hodgkin-like cells (HLC) have been described in a variety of non-Hodgkin lymphomas (NHL) including chronic lymphocytic leukemia (CLL) and peripheral T-cell lymphoma (PTCL). There have been rare reports in the Japanese population of human T-cell lymphotrophic virus-1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATLL) harboring HLC; however, no similar cases have been described in western patients. We report a 53-year-old African-American man that presented with progressive weakness and lethargy, and was found to have generalized lymphadenopathy and hypercalcemia. A lymph node biopsy showed involvement by ATLL with scattered Epstein-Barr virus (EBV)-positive cells, some of which resembled Hodgkin cells that had a B-cell phenotype, consistent with an Epstein-Barr virus-lymphoproliferative disorder (LPD). The patient had stage 4 disease with bone marrow involvement. In light of the associated B-cell lymphoproliferative process, the patient was treated with six cycles of intensive chemotherapy that targeted both the ATLL and the EBV-LPD that resulted in a complete response. An awareness of the association of EBV-LPD with Hodgkin-like cells in the context of ATLL is necessary to avoid potential misdiagnosis and to aid in therapeutic decisions. PMID:21315416

Venkataraman, Girish; Berkowitz, Jonathan; Morris, John C.; Janik, John E.; Raffeld, Mark A.; Pittaluga, Stefania

2011-01-01

253

Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts.  

PubMed

The bone marrow niche is thought to act as a permissive microenvironment required for emergence or progression of hematologic cancers. We hypothesized that osteoblasts, components of the niche involved in hematopoietic stem cell (HSC) function, influence the fate of leukemic blasts. We show that osteoblast numbers decrease by 55% in myelodysplasia and acute myeloid leukemia patients. Further, genetic depletion of osteoblasts in mouse models of acute leukemia increased circulating blasts and tumor engraftment in the marrow and spleen leading to higher tumor burden and shorter survival. Myelopoiesis increased and was coupled with a reduction in B lymphopoiesis and compromised erythropoiesis, suggesting that hematopoietic lineage/progression was altered. Treatment of mice with acute myeloid or lymphoblastic leukemia with a pharmacologic inhibitor of the synthesis of duodenal serotonin, a hormone suppressing osteoblast numbers, inhibited loss of osteoblasts. Maintenance of the osteoblast pool restored normal marrow function, reduced tumor burden, and prolonged survival. Leukemia prevention was attributable to maintenance of osteoblast numbers because inhibition of serotonin receptors alone in leukemic blasts did not affect leukemia progression. These results suggest that osteoblasts play a fundamental role in propagating leukemia in the marrow and may be a therapeutic target to induce hostility of the niche to leukemia blasts. PMID:25139351

Krevvata, Maria; Silva, Barbara C; Manavalan, John S; Galan-Diez, Marta; Kode, Aruna; Matthews, Brya Grace; Park, David; Zhang, Chiyuan A; Galili, Naomi; Nickolas, Thomas L; Dempster, David W; Dougall, William; Teruya-Feldstein, Julie; Economides, Aris N; Kalajzic, Ivo; Raza, Azra; Berman, Ellin; Mukherjee, Siddhartha; Bhagat, Govind; Kousteni, Stavroula

2014-10-30

254

Stereotyped B-cell receptors in chronic lymphocytic leukemia.  

PubMed

Over the last decade, immunogenetic analysis of B-cell receptor immunoglobulins (BcR IGs) has proved to be a particularly fruitful field in chronic lymphocytic leukemia (CLL), not only for understanding disease pathogenesis but also for discriminating clinical subgroups with markedly distinct course and outcome. Of utmost importance was the identification of quasi-identical BcR IGs among unrelated patients with CLL, fittingly coined as "stereotypy," that set the wheels in motion for unraveling the role of antigen(s) in the selection and expansion of the leukemic clones. The categorization of CLL clones into "subsets" according to shared BcR IG structural characteristics provided a compartmentalized view of this otherwise heterogeneous disease, which eventually led to defining strikingly homogeneous groups of patients in terms of: (i) functional properties of the clonal BcR IGs, e.g. BcR reactivity and signaling; (ii) clonal genetic landscape, e.g. genomic aberrations, gene expression/methylation profiles, microRNA signatures; and (iii) clinical course and outcome. The remarkable restriction of the CLL IG gene repertoire, resulting to a great degree from the high impact of BcR IG stereotypy, may also prompt speculations regarding CLL ontogenesis. Overall, the BcR IG molecule justifiably lies at the heart of CLL clinical research, holding the promise of subset-tailored therapies. PMID:24397617

Agathangelidis, Andreas; Vardi, Anna; Baliakas, Panagiotis; Stamatopoulos, Kostas

2014-10-01

255

Xanthoangelol, a major chalcone constituent of Angelica keiskei, induces apoptosis in neuroblastoma and leukemia cells.  

PubMed

Xanthoangelol, a major chalcone constituent of the stem exudates of Angelica keiskei, was evaluated for cell toxicity and apoptosis-inducing activity in human neuroblastoma (IMR-32) and leukemia (Jurkat) cells. Xanthoangelol concentration-dependently reduced the survival rates of both cell lines as revealed by the trypan blue exclusion test. Early apoptosis induced by 4 h incubation with xanthoangelol was detected using flow cytometry after double-staining with annexin V and propidium iodide (PI). Western blot analysis showed that xanthoangelol markedly reduced the level of precursor caspase-3 and increased the level of cleaved caspase-3, but Bax and Bcl-2 proteins were not affected. These results suggest that xanthoangelol induces apoptotic cell death by activatation of caspase-3 in neuroblastoma and leukemia cells through a mechanism that does not involve Bax/Bcl-2 signal transduction. Therefore, xanthoangelol may be applicable as an effective drug for treatment of neuroblastoma and leukemia. PMID:16079483

Tabata, Keiichi; Motani, Kou; Takayanagi, Noriya; Nishimura, Reiko; Asami, Satoru; Kimura, Yumiko; Ukiya, Motohiko; Hasegawa, Daisuke; Akihisa, Toshihiro; Suzuki, Takashi

2005-08-01

256

Donor T Cells After Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies  

ClinicalTrials.gov

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

2014-10-14

257

Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies  

ClinicalTrials.gov

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Aplastic Anemia; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Congenital Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Paroxysmal Nocturnal Hemoglobinuria; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Severe Combined Immunodeficiency; Severe Congenital Neutropenia; Shwachman-Diamond Syndrome; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Waldenstrom Macroglobulinemia; Wiskott-Aldrich Syndrome

2015-02-26

258

Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer  

ClinicalTrials.gov

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Melanoma; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer

2013-01-09

259

Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity?  

PubMed Central

Acute leukemias are the most common cancer in childhood and characterized by the uncontrolled production of hematopoietic precursor cells of the lymphoid or myeloid series within the bone marrow. Even when a relatively high efficiency of therapeutic agents has increased the overall survival rates in the last years, factors such as cell lineage switching and the rise of mixed lineages at relapses often change the prognosis of the illness. During lineage switching, conversions from lymphoblastic leukemia to myeloid leukemia, or vice versa, are recorded. The central mechanisms involved in these phenomena remain undefined, but recent studies suggest that lineage commitment of plastic hematopoietic progenitors may be multidirectional and reversible upon specific signals provided by both intrinsic and environmental cues. In this paper, we focus on the current knowledge about cell heterogeneity and the lineage switch resulting from leukemic cells plasticity. A number of hypothetical mechanisms that may inspire changes in cell fate decisions are highlighted. Understanding the plasticity of leukemia initiating cells might be fundamental to unravel the pathogenesis of lineage switch in acute leukemias and will illuminate the importance of a flexible hematopoietic development. PMID:22852088

Dorantes-Acosta, Elisa; Pelayo, Rosana

2012-01-01

260

Black hairy tongue syndrome.  

PubMed

Black hairy tongue (BHT) is a benign medical condition characterized by elongated filiform lingual papillae with typical carpet-like appearance of the dorsum of the tongue. Its prevalence varies geographically, typically ranging from 0.6% to 11.3%. Known predisposing factors include smoking, excessive coffee/black tea consumption, poor oral hygiene, trigeminal neuralgia, general debilitation, xerostomia, and medication use. Clinical presentation varies but is typically asymptomatic, although aesthetic concerns are common. Differential diagnosis includes pseudo-BHT, acanthosis nigricans, oral hairy leukoplakia, pigmented fungiform papillae of the tongue, and congenital melanocytic/melanotic nevi/macules. Clinical diagnosis relies on visual observation, detailed history taking, and occasionally microscopic evaluation. Treatment involves identification and discontinuation of the offending agent, modifications of chronic predisposing factors, patient's re-assurance to the benign nature of the condition, and maintenance of adequate oral hygiene with gentle debridement to promote desquamation. Complications of BHT (burning mouth syndrome, halitosis, nausea, gagging, dysgeusia) typically respond to therapy. Prognosis is excellent with treatment of underlying medical conditions. BHT remains an important medical condition which may result in additional burden on the patient and health care system and requires appropriate prevention, recognition and treatment. PMID:25152586

Gurvits, Grigoriy E; Tan, Amy

2014-08-21

261

Black hairy tongue syndrome  

PubMed Central

Black hairy tongue (BHT) is a benign medical condition characterized by elongated filiform lingual papillae with typical carpet-like appearance of the dorsum of the tongue. Its prevalence varies geographically, typically ranging from 0.6% to 11.3%. Known predisposing factors include smoking, excessive coffee/black tea consumption, poor oral hygiene, trigeminal neuralgia, general debilitation, xerostomia, and medication use. Clinical presentation varies but is typically asymptomatic, although aesthetic concerns are common. Differential diagnosis includes pseudo-BHT, acanthosis nigricans, oral hairy leukoplakia, pigmented fungiform papillae of the tongue, and congenital melanocytic/melanotic nevi/macules. Clinical diagnosis relies on visual observation, detailed history taking, and occasionally microscopic evaluation. Treatment involves identification and discontinuation of the offending agent, modifications of chronic predisposing factors, patient’s re-assurance to the benign nature of the condition, and maintenance of adequate oral hygiene with gentle debridement to promote desquamation. Complications of BHT (burning mouth syndrome, halitosis, nausea, gagging, dysgeusia) typically respond to therapy. Prognosis is excellent with treatment of underlying medical conditions. BHT remains an important medical condition which may result in additional burden on the patient and health care system and requires appropriate prevention, recognition and treatment. PMID:25152586

Gurvits, Grigoriy E; Tan, Amy

2014-01-01

262

p27kip1 maintains a subset of leukemia stem cells in the quiescent state in murine MLL-leukemia.  

PubMed

MLL (mixed-lineage leukemia)-fusion genes induce the development of leukemia through deregulation of normal MLL target genes, such as HOXA9 and MEIS1. Both HOXA9 and MEIS1 are required for MLL-fusion gene-induced leukemogenesis. Co-expression of HOXA9 and MEIS1 induces acute myeloid leukemia (AML) similar to that seen in mice in which MLL-fusion genes are over-expressed. p27(kip1) (p27 hereafter), a negative regulator of the cell cycle, has also been defined as an MLL target, the expression of which is up-regulated in MLL leukemic cells (LCs). To investigate whether p27 plays a role in the pathogenesis of MLL-leukemia, we examined the effects of p27 deletion (p27(-/-)) on MLL-AF9 (MA9)-induced murine AML development. HOXA9/MEIS1 (H/M)-induced, p27 wild-type (p27(+/+)) and p27(-/-) AML were studied in parallel as controls. We found that LCs from both MA9-AML and H/M-AML can be separated into three fractions, a CD117(-)CD11b(hi) differentiated fraction as well as CD117(+)CD11b(hi) and CD117(+)CD11b(lo), two less differentiated fractions. The CD117(+)CD11b(lo) fraction, comprising only 1-3% of total LCs, expresses higher levels of early hematopoietic progenitor markers but lower levels of mature myeloid cell markers compared to other populations of LCs. p27 is expressed and is required for maintaining the quiescent and drug-resistant states of the CD117(+)CD11b(lo) fraction of MA9-LCs but not of H/M-LCs. p27 deletion significantly compromises the leukemogenic capacity of CD117(+)CD11b(lo) MA9-LCs by reducing the frequency of leukemic stem cells (LSCs) but does not do so in H/M-LCs. In addition, we found that p27 is highly expressed and required for cell cycle arrest in the CD117(-)CD11b(hi) fraction in both types of LCs. Furthermore, we found that c-Myc expression is required for maintaining LCs in an undifferentiated state independently of proliferation. We concluded that p27 represses the proliferation of LCs, which is specifically required for maintaining the quiescent and drug-resistant states of a small subset of MA9-LSCs in collaboration with the differentiation blockage function of c-Myc. PMID:23988911

Zhang, Jun; Seet, Christopher S; Sun, Clare; Li, Jing; You, Dewen; Volk, Andrew; Breslin, Peter; Li, Xingyu; Wei, Wei; Qian, Zhijian; Zeleznik-Le, Nancy J; Zhang, Zhou; Zhang, Jiwang

2013-12-01

263

p27kip1 Maintains a Subset of Leukemia Stem Cells in the Quiescent State in Murine MLL-Leukemia  

PubMed Central

MLL (mixed-lineage leukemia)-fusion genes induce the development of leukemia through deregulation of normal MLL target genes, such as HOXA9 and MEIS1. Both HOXA9 and MEIS1 are required for MLL-fusion gene-induced leukemogenesis. Co-expression of HOXA9 and MEIS1 induces acute myeloid leukemia (AML) similar to that seen in mice in which MLL-fusion genes are over-expressed. p27kip1 (p27 hereafter), a negative regulator of the cell cycle, has also been defined as an MLL target, the expression of which is up-regulated in MLL leukemic cells (LCs). To investigate whether p27 plays a role in the pathogenesis of MLL-leukemia, we examined the effects of p27 deletion (p27-/-) on MLL-AF9 (MA9)-induced murine AML development. HOXA9/MEIS1 (H/M)-induced, p27 wild-type (p27+/+) and p27-/- AML were studied in parallel as controls. We found that LCs from both MA9-AML and H/M-AML can be separated into three fractions, a CD117-CD11bhi differentiated fraction as well as CD117+CD11bhi and CD117+CD11blo, two less differentiated fractions. The CD117+CD11blo fraction, comprising only 1-3% of total LCs, expresses higher levels of early hematopoietic progenitor markers but lower levels of mature myeloid cell markers compared to other populations of LCs. p27 is expressed and is required for maintaining the quiescent and drug-resistant states of the CD117+CD11blo fraction of MA9-LCs but not of H/M-LCs. p27 deletion significantly compromises the leukemogenic capacity of CD117+CD11blo MA9-LCs by reducing the frequency of leukemic stem cells (LSCs) but does not do so in H/M-LCs. In addition, we found that p27 is highly expressed and required for cell cycle arrest in the CD117-CD11bhi fraction in both types of LCs. Furthermore, we found that c-Myc expression is required for maintaining LCs in an undifferentiated state independently of proliferation. We concluded that p27 represses the proliferation of LCs, which is specifically required for maintaining the quiescent and drug-resistant states of a small subset of MA9-LSCs in collaboration with the differentiation blockage function of c-Myc. PMID:23988911

Zhang, Jun; Seet, Christopher; Sun, Clare; Li, Jing; You, Dewen; Volk, Andrew; Breslin, Peter; Li, Xingyu; Wei, Wei; Qian, Zhijian; Zeleznik-Le, Nancy J.; Zhang, Zhou; Zhang, Jiwang

2013-01-01

264

Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection  

ClinicalTrials.gov

Adult B Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; HIV Infection; Intraocular Lymphoma; Multicentric Angiofollicular Lymphoid Hyperplasia; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Plasma Cell Myeloma; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

2015-03-05

265

Differentiation induction in non-lymphocytic leukemia cells upon treatment with mycophenolate mofetil.  

PubMed

Inosine 5'-monophosphate (IMP) dehydrogenase catalyzes the rate-limiting reaction of guanine nucleotide biosynthesis and has been implicated in the reaction of cell growth and differentiation. We investigated the ability of mycophenolate mofetil, a prodrug of mycophenolic acid, to induce differentiation in HL-60 and U937 leukemic cells as well as in fresh leukemia cells from patients with non-lymphocytic leukemia. Treatment with mycophenolate mofetil reduced the intracellular guanosine 5'-triphosphate (GTP) levels and induced morphologic and functional differentiation in HL-60 and U937 cells dose-dependently. HL-60 and U937 cells developed macrophage-like cytoplasm as well as the expression of CD11b and CD14 antigens and the ability to oxidize nitroblue tetrazorium (NBT). These changes became evident when the intracellular GTP levels decreased to approximately 20-30% of the untreated control level and were abrogated by the addition of guanosine. In the fresh leukemic cells, differentiation induction was shown in the cells derived from seven of 13 patients. The fresh leukemia cells responding to mycophenolate mofetil revealed significant higher positivity to CD11b, CD14, and NBT before treatment and significantly reduced intracellular GTP levels after treatment compared to the non-responding cells. These findings suggest that mycophenolate mofetil induces differentiation in HL-60 and U937 cells and some fresh leukemia cells with moderate tendency to maturation, by causing a decrease in the intracellular GTP levels. Mycophenolate mofetil could be a promising differentiation inducer in vivo. PMID:10978780

Inai, K; Tsutani, H; Yamauchi, T; Fukushima, T; Iwasaki, H; Imamura, S; Wano, Y; Nemoto, Y; Naiki, H; Ueda, T

2000-09-01

266

Induction by Bufalin of Differentiation of Human Leukemia Cells HL60, U937, and ML1 toward Macrophage\\/Monocyte-like Cells and Its Potent Synergistic Effect on the Differentiation of Human Leukemia Cells in Combination with Other Inducers  

Microsoft Academic Search

We have recently demonstrated that bufalin is a new potent inducer of the differentiation of human myeloid leukemia cells. The present work was carried out to examine further the effect of bufalin on the growth and characteristics of human leukemia-derived cell lines U937, Mil. and HL60. At concentrations of 5-10 IIM,bufalin decreased the growth of Mil cells preferentially at the

Lisha Zhang; Takemi Yoshida; Yukio Kuroiwa

267

Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia  

ClinicalTrials.gov

Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Adult L1 Acute Lymphoblastic Leukemia; Adult L2 Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

2015-03-23

268

Cryopreservation of autologous marrow grafts in acute leukemia: survival of in vivo clonogenic leukemic cells and normal hemopoietic stem cells.  

PubMed

The survival of pluripotent hemopoietic stem cells and in vivo clonogenic leukemic cells after cryopreservation was determined in a rat model for human acute myelocytic leukemia (BNML). These stem cell populations can be selectively quantified with modified spleen colony assays (day 8 and day 12 CFU-S; LCFU-S). It appeared that the most primitive rat hemopoietic stem cell (day 12 CFU-S) was significantly less vulnerable to the freezing and thawing procedure as compared with the clonogenic leukemic cell (30% and 1.4% survival, respectively; p = 0.0026). Survival of the day 8 CFU-S population fell between those percentages (8.6%). In view of autologous bone marrow transplantation (ABMT), an attempt was made to extrapolate these and previously reported BNML rat data to man. Taking into account that a) only 1% of the clonogenic leukemic cells survive cryopreservation; b) the fraction of clonogenic leukemic cells in man is approximately 0.001; c) leukemic cells reinfused with the autologous marrow graft may lodge at sites unfavourable for growth; and d) supralethal high-dose chemoradiotherapy significantly hampers the regrowth of leukemia, it becomes rather unlikely that leukemic cells in the autologous marrow graft significantly contribute to a leukemia relapse after ABMT. Therefore, residual leukemia in the host surviving high-dose chemoradiotherapy is the most crucial factor as regards the final outcome of ABMT in acute leukemia. PMID:2659904

Hagenbeek, A; Martens, A C

1989-07-01

269

Occupational exposure to formaldehyde, hematotoxicity and leukemia-specific chromosome changes in cultured myeloid progenitor cells  

PubMed Central

There are concerns about the health effects of formaldehyde exposure, including carcinogenicity, in light of elevated indoor air levels in new homes and occupational exposures experienced by workers in health care, embalming, manufacturing and other industries. Epidemiological studies suggest that formaldehyde exposure is associated with an increased risk of leukemia. However, the biological plausibility of these findings has been questioned because limited information is available on formaldehyde’s ability to disrupt hematopoietic function. Our objective was to determine if formaldehyde exposure disrupts hematopoietic function and produces leukemia-related chromosome changes in exposed humans. We examined the ability of formaldehyde to disrupt hematopoiesis in a study of 94 workers in China (43 exposed to formaldehyde and 51 frequency-matched controls) by measuring complete blood counts and peripheral stem/progenitor cell colony formation. Further, myeloid progenitor cells, the target for leukemogenesis, were cultured from the workers to quantify the level of leukemia-specific chromosome changes, including monosomy 7 and trisomy 8, in metaphase spreads of these cells. Among exposed workers, peripheral blood cell counts were significantly lowered in a manner consistent with toxic effects on the bone marrow and leukemia-specific chromosome changes were significantly elevated in myeloid blood progenitor cells. These findings suggest that formaldehyde exposure can have an adverse impact on the hematopoietic system and that leukemia induction by formaldehyde is biologically plausible, which heightens concerns about its leukemogenic potential from occupational and environmental exposures. PMID:20056626

Zhang, Luoping; Tang, Xiaojiang; Rothman, Nathaniel; Vermeulen, Roel; Ji, Zhiying; Shen, Min; Qiu, Chuangyi; Guo, Weihong; Liu, Songwang; Reiss, Boris; Laura Beane, Freeman; Ge, Yichen; Hubbard, Alan E.; Hua, Ming; Blair, Aaron; Galvan, Noe; Ruan, Xiaolin; Alter, Blanche P.; Xin, Kerry X.; Li, Senhua; Moore, Lee E.; Kim, Sungkyoon; Xie, Yuxuan; Hayes, Richard B.; Azuma, Mariko; Hauptmann, Michael; Xiong, Jun; Stewart, Patricia; Li, Laiyu; Rappaport, Stephen M.; Huang, Hanlin; Fraumeni, Joseph F.; Smith, Martyn T.; Lan, Qing

2010-01-01

270

Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant  

ClinicalTrials.gov

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cytomegalovirus Infection; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Isolated Plasmacytoma of Bone; Monoclonal Gammopathy of Undetermined Significance; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Primary Myelofibrosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Multiple Myeloma; Stage I Small Lymphocytic Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Multiple Myeloma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cu

2015-01-09

271

Differential mechanisms of cell death induction via delivery of therapeutic nanoliposomal ceramide in leukemias  

NASA Astrophysics Data System (ADS)

Large granular lymphocyte (LGL) leukemia is a rare lymphoproliferative malignancy that involves blood, bone marrow and spleen infiltration. Clinically, LGL leukemia can manifest as a chronic lymphocytosis or as an aggressive leukemia that is fatal within a short period of time. A segment of LGL leukemia patients are unresponsive to immunosuppressive therapy and currently there is no known curative treatment for this disease. Another hematological malignancy, chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in adults in Western countries and accounts for approximately 30% of all diagnosed leukemia cases. Around 95% of all CLL cases involve clonal expansion and abnormal proliferation of neoplastic B lymphocytes in lymphoid organs, bone marrow and peripheral blood. Similar to LGL leukemia, CLL is also incurable with current therapies. Therefore, this represents a need for new therapeutic approaches for treatment of these diseases. Recent advances in nanotechnology have illustrated the feasibility of generating nanoliposomes that encapsulate hydrophobic compounds, like ceramide, to facilitate treatment of LGL leukemia and CLL. Ceramide is an anti-proliferative sphingolipid metabolite that has been shown to selectively induce cell death in cancer cells. However, the use of ceramide as a chemotherapeutic agent is limited due to hydrophobicity. While it is understood how nanoliposomal ceramide induces cell death in several types of cancers and hematological malignancies, the effect of nanoliposomal ceramide treatment in LGL leukemia and CLL remains unclear. In this study, we investigate the differential mechanisms of cell death induction following nanoliposomal C6-ceramide treatment in both LGL leukemia and CLL. We show that nanoliposomal C6-ceramide displays minimal cytotoxicity in normal donors. peripheral blood mononuclear cells (PBMCs) and is a well-tolerated therapy during in vivo treatment in these leukemia models. To further examine this mechanism of selectivity, we utilize CLL as a cancer model which has an increased dependency on glycolysis. As most tumors exhibit a preferential switch to glycolysis, as described in the "Warburg effect," we hypothesize that ceramide nanoliposomes selectively target this activated glycolytic pathway in cancer. We demonstrate that nanoliposomal ceramide inhibits both the RNA and protein expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an intermediate enzyme in the glycolytic pathway, which is overexpressed in a subset of CLL patients. Taken together, our results suggest that C6-ceramide nanoliposomes preferentially inhibit the enhanced metabolism of glucose in leukemic CLL cells, which results in induction of cell death. We conclude that selective inhibition of the glycolytic pathway in CLL cells with nanoliposomal C6-ceramide could potentially be an effective therapy for this leukemia by targeting the Warburg effect. In addition, we conclude that nanoliposomal C6-ceramide could also be an effective therapy for patients with LGL leukemia. Collectively, the results of this dissertation emphasize exploitation of sphingolipids and sphingolipid metabolism in design and development of novel chemotherapeutics.

Ryland, Lindsay K.

272

Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer  

ClinicalTrials.gov

Acute Undifferentiated Leukemia; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Renal Cell Cancer; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

2014-08-01

273

Metabolic Effects of Acute Thiamine Depletion Are Reversed by Rapamycin in Breast and Leukemia Cells  

PubMed Central

Thiamine-dependent enzymes (TDEs) control metabolic pathways that are frequently altered in cancer and therefore present cancer-relevant targets. We have previously shown that the recombinant enzyme thiaminase cleaves and depletes intracellular thiamine, has growth inhibitory activity against leukemia and breast cancer cell lines, and that its growth inhibitory effects were reversed in leukemia cell lines by rapamycin. Now, we first show further evidence of thiaminase therapeutic potential by demonstrating its activity against breast and leukemia xenografts, and against a primary leukemia xenograft. We therefore further explored the metabolic effects of thiaminase in combination with rapamycin in leukemia and breast cell lines. Thiaminase decreased oxygen consumption rate and increased extracellular acidification rate, consistent with the inhibitory effect of acute thiamine depletion on the activity of the TDEs pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes; these effects were reversed by rapamycin. Metabolomic studies demonstrated intracellular thiamine depletion and the presence of the thiazole cleavage product in thiaminase-treated cells, providing validation of the experimental procedures. Accumulation of ribose and ribulose in both cell lines support the thiaminase-mediated suppression of the TDE transketolase. Interestingly, thiaminase suppression of another TDE, branched chain amino ketoacid dehydrogenase (BCKDH), showed very different patterns in the two cell lines: in RS4 leukemia cells it led to an increase in BCKDH substrates, and in MCF-7 breast cancer cells it led to a decrease in BCKDH products. Immunoblot analyses showed corresponding differences in expression of BCKDH pathway enzymes, and partial protection of thiaminase growth inhibition by gabapentin indicated that BCKDH inhibition may be a mechanism of thiaminase-mediated toxicity. Surprisingly, most of thiaminase-mediated metabolomic effects were also reversed by rapamycin. Thus, these studies demonstrate that acute intracellular thiamine depletion by recombinant thiaminase results in metabolic changes in thiamine-dependent metabolism, and demonstrate a previously unrecognized role of mTOR signaling in the regulation of thiamine-dependent metabolism. PMID:24454921

Liu, Shuqian; Miriyala, Sumitra; Keaton, Mignon A.; Jordan, Craig T.; Wiedl, Christina; Clair, Daret K. St.; Moscow, Jeffrey A.

2014-01-01

274

Loss of mismatched HLA in myeloid/NK cell precursor acute leukemia relapse after T cell-replete haploidentical hematopoietic stem cell transplantation.  

PubMed

Myeloid/natural killer cell precursor acute leukemia (MNKL) is an aggressive disease with a high relapse rate even after allogeneic hematopoietic stem cell transplantation (SCT). We report a patient with MNKL who had a donor lymphocyte infusion (DLI) for relapse after T cell-replete human leukocyte antigen (HLA)-haploidentical SCT, but relapsed again 20 months later with loss of mismatched HLA. This case suggests that a strong graft-versus-leukemia effect of haploidentical SCT can be expected in MNKL patients. In the haploidentical setting, DLI should be considered for patients with relapsed leukemia whose leukemic cells have not lost HLA cell surface expression. PMID:24464971

Kobayashi, Shogo; Kikuta, Atsushi; Ito, Masaki; Sano, Hideki; Mochizuki, Kazuhiro; Akaihata, Mitsuko; Waragai, Tomoko; Ohara, Yoshihiro; Ogawa, Chitose; Ono, Satoshi; Ohto, Hitoshi; Hosoya, Mitsuaki

2014-10-01

275

Enhancement of fludarabine sensitivity by all-trans-retinoic acid in chronic lymphocytic leukemia cells  

PubMed Central

Background A subset of patients with fludarabine-resistant chronic lymphocytic leukemia has previously been shown to express elevated intracellular levels of the concentrative high-affinity fludarabine transporter hCNT3, without any detectable related activity. We have recently shown that all-trans-retinoic acid is capable of inducing hCNT3 trafficking to plasma membrane in the MEC1 cell line. We, therefore, evaluated the effect of all-trans-retinoic acid on hCNT3 in primary chronic lymphocytic leukemia cells as a suitable mechanism to improve fludarabine-based therapy of chronic lymphocytic leukemia. Design and Methods Cells from 23 chronic lymphocytic leukemia patients wild-type for P53 were analyzed for ex vivo sensitivity to fludarabine. hCNT3 activity in chronic lymphocytic leukemia cell samples was evaluated by measuring the uptake of [8-3H]-fludarabine. The amounts of transforming growth factor-?1 and hCNT3 messenger RNA were analyzed by real-time polymerase chain reaction. The effect of all-trans-retinoic acid on hCNT3 subcellular localization was analyzed by confocal microscopy and its effect on fludarabine-induced apoptosis was evaluated by flow cytometry analysis using annexin V staining. Results Chronic lymphocytic leukemia cases showing higher ex vivo basal sensitivity to fludarabine also had a greater basal hCNT3-associated fludarabine uptake capacity compared to the subset of patients showing ex vivo resistance to the drug. hCNT3 transporter activity in chronic lymphocytic leukemia cells from the latter patients was either negligible or absent. Treatment of the fludarabine-resistant subset of chronic lymphocytic leukemia cells with all-trans-retinoic acid induced increased fludarabine transport via hCNT3 which was associated with a significant increase in fludarabine sensitivity. Conclusions Improvement of ex vivo fludarabine sensitivity in chronic lymphocytic leukemia cells is associated with increased hCNT3 activity after all-trans-retinoic acid treatment. PMID:22180426

Fernández-Calotti, Paula X.; Lopez-Guerra, Mónica; Colomer, Dolors; Pastor-Anglada, Marçal

2012-01-01

276

Fatal Syndrome in Mice Engrafted with Cells Producing High Levels of the Leukemia Inhibitory Factor  

Microsoft Academic Search

Cells of the murine hemopoietic cell line FDC-P1 were multiply infected with a retroviral construct containing cDNA encoding the leukemia inhibitory factor (LIF) to produce cells secreting high levels of LIF. Injection of these cells to unirradiated or irradiated syngeneic DBA\\/2 mice resulted in animals engrafted with LIF-producing cells in the marrow, spleen, and lymph nodes and with elevated serum

D. Metcalf; D. P. Gearing

1989-01-01

277

Aspects of hairy black holes  

NASA Astrophysics Data System (ADS)

We review the existence of exact hairy black holes in asymptotically flat, anti-de Sitter and de Sitter space-times. We briefly discuss the issue of stability and the charging of the black holes with a Maxwell field.

Anabalón, Andrés; Astefanesei, Dumitru

2015-03-01

278

Frequent upregulation of MYC in plasma cell leukemia.  

PubMed

Plasma cell leukemia (PCL) is a rare form of monoclonal gammopathy, which can originate de novo or evolve from multiple myeloma (MM) as a terminal leukemic phase. Previous cytogenetic studies of PCL have reported the presence of complex karyotypes with involvement of multiple unidentified chromosomal regions. We report here the analysis of 12 PCL (10 primary and two secondary) by metaphase and FISH analysis combined with oligonucleotide array data (244 k, Agilent). Interphase-FISH results were compared with those from a series of 861 newly diagnosed patients with MM. Cytogenetic analysis was successful on 11 patients, all of whom showed clonal chromosomal abnormalities. Compared with MM, t(11;14)(q13;q32) (42% versus 15%; P = 0.027) and t(14;16)(q32;q23) (25% versus 4%; P = 0.010) were more frequent in PCL, although neither the specific partner chromosome involved in the IgH translocation nor the ploidy status predicted for survival. Chromosomes 1, 8, 13, and 16 showed the highest number of copy number alterations with 8q24 being the chromosomal region most frequently involved. In eight of 12 patients we found abnormalities (translocations, one amplification, small deletions, and duplications) that directly targeted or were very close to MYC. Only four of these changes were detected by routine FISH analysis using commercial probes with the others exclusively detected by arrays. Quantitative reverse transcription polymerase chain reaction demonstrated that these different abnormalities were associated with increased levels of MYC mRNA. We conclude that MYC dysregulation by complex mechanisms is one of the major molecular events in the oncogenesis of PCL. PMID:19396865

Chiecchio, Laura; Dagrada, Gian Paolo; White, Helen E; Towsend, Mark R; Protheroe, Rebecca K M; Cheung, Kan Luk; Stockley, David M; Orchard, Kim H; Cross, Nicholas C P; Harrison, Christine J; Ross, Fiona M

2009-07-01

279

Induction of apoptosis in acute lymphoblastic leukemia cells by isolated fractions from strawberries  

Technology Transfer Automated Retrieval System (TEKTRAN)

Strawberries contain phytochemicals that have anti-inflammatory and anti-cancer activity. We investigated the ability of isolated fractions from strawberry extracts to induce apoptotic cell death in three pre-B acute lymphoblastic leukemia (ALL) lines, including SEM and RS4;11 cell lines derived fr...

280

Leukemia . Author manuscript Follicular lymphoma cell niche: identification of a preeminent  

E-print Network

Follicular lymphoma (FL) is the most common indolent non-Hodgkin s lymphoma and remains virtually incurableLeukemia . Author manuscript Page /1 12 Follicular lymphoma cell niche: identification equally to this work Abstract Follicular lymphoma (FL) B cells contract tight connections

Boyer, Edmond

281

Reproductive fitness advantage of BCRABL expressing leukemia cells Arne Traulsen a  

E-print Network

Reproductive fitness advantage of BCR­ABL expressing leukemia cells Arne Traulsen a , Jorge M Keywords: Cancer evolution Oncogenes Mutation fitness BCR­ABL Cancer dynamics a b s t r a c t Mutations in oncogenes and tumor suppressor genes confer a fitness advantage to cells that can lead to cancer. The tumor

Traulsen, Arne

282

Induction of Differentiation in Human Promyelocytic Leukemia Cells by Tumor Promoters  

Microsoft Academic Search

Phorbol diester tumor promoters and the promoter mezerein convert human promyelocytic leukemia cells in culture into adherent, nonproliferating cells with many of the characteristics of macrophages. Other types of promoters such as anthralin, phenobarbital, and saccharin do not have this effect. Various compounds that can inhibit some of the biological and biochemical effects of tumor promoters do not interfere with

Giovanni Rovera; Thomas G. O'Brien; Leila Diamond

1979-01-01

283

Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies  

ClinicalTrials.gov

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

2014-12-29

284

Leukemia mortality by cell type in petroleum workers with potential exposure to benzene.  

PubMed Central

Workers in the petroleum industry are potentially exposed to a variety of petrochemicals, including benzene or benzene-containing liquids. Although a large number of studies of petroleum workers have been conducted to examine leukemia and other cancer risks, few existing studies have investigated cell-type-specific leukemias. One of the major reasons for the lack of cell-type-specific analysis was the small number of deaths by cell type in individual studies. In the present investigation, all cohort studies of petroleum workers in the United States and the United Kingdom were combined into a single database for cell-type-specific leukemia analysis. The majority of these workers were petroleum refinery employees, but production, pipeline, and distribution workers in the petroleum industry were also included. The combined cohort consisted of more than 208,000 petroleum workers, who contributed more than 4.6 million person-years of observation. Based on a meta-analysis of the combined data, cell-type-specific leukemia risks were expressed in terms of standardized mortality ratios (meta-SMRs). The meta-SMR for acute myeloid leukemia was 0.96. The lack of an increase of acute myeloid leukemia was attributed to the low levels of benzene exposure in the petroleum industry, particularly in comparison to benzene exposure levels in some previous studies of workers in other industries, who had been found to experience an increased risk of acute myeloid leukemia. Similarly, no increase in chronic myeloid, acute lymphocytic, or chronic lymphocytic leukemias was found in petroleum workers (meta-SMRs of 0.89, 1.16, and 0.84, respectively). Stratified meta-analyses restricted to refinery studies or to studies with at least 15 years of follow-up yielded similar results. The findings of the present investigation are consistent with those from several recent case-control studies of cell-type-specific leukemia. Patterns and levels of benzene exposure in the petroleum industry are reviewed. The results of the present epidemiologic investigation are discussed in conjunction with recent advances in leukemogenesis from other scientific disciplines. PMID:9118924

Raabe, G K; Wong, O

1996-01-01

285

Signal transduction pathways and transcription factors triggered by arsenic trioxide in leukemia cells  

SciTech Connect

Arsenic trioxide (As{sub 2}O{sub 3}) is widely used to treat acute promyelocytic leukemia (APL). Several lines of evidence have indicated that As{sub 2}O{sub 3} affects signal transduction and transactivation of transcription factors, resulting in the stimulation of apoptosis in leukemia cells, because some transcription factors are reported to associate with the redox condition of the cells, and arsenicals cause oxidative stress. Thus, the disturbance and activation of the cellular signaling pathway and transcription factors due to reactive oxygen species (ROS) generation during arsenic exposure may explain the ability of As{sub 2}O{sub 3} to induce a complete remission in relapsed APL patients. In this report, we review recent findings on ROS generation and alterations in signal transduction and in transactivation of transcription factors during As{sub 2}O{sub 3} exposure in leukemia cells.

Sumi, Daigo, E-mail: sdaigo@ph.bunri-u.ac.j [Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180, Yamashiro-cho, Tokushima-city, Tokushima 770-8514 (Japan); Shinkai, Yasuhiro; Kumagai, Yoshito [Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575 (Japan)

2010-05-01

286

In-vitro infection of chronic lymphocytic leukemia cells by Epstein-Barr virus (EBV).  

PubMed

We sought to determine the potential of infecting lymphoid cells from patients with chronic leukemia (CLL) with Epstein-Barr virus (EBV) by testing for EBV receptors (EBVR) by flow cytometry, assessing for infectability of these cells by culturing with B95-8-derived virus, and staining for EB nuclear-associated antigens (EBNA) at various times post-infection. EBVR were present on 54-91% of lymphoid cells in seven cases of CLL and on 46% of prolymphocytic leukemia cells. Dynamic changes regarding EBNA positivity, morphology, and viability occurred post-infection with the virus. On day 2 only a few EBNA-positive lymphoblasts were observed. On days 11-21 positivity increased from 2 to 34% of cells. Simultaneously, the viable cell number declined to approximately 1/10th of original number. A significant proportion of the EBNA-positive cells corresponded to the original CLL cells. In 3 of 7 cases of CLL a Pan T-cell phenotype was demonstrated by Leu-1 monoclonal antibody testing. The infected cells did not react with two monoclonal antibodies, EBV-CS 1 and 4, which react with B-cell lymphoblastoid cell lines (B-LCL). Moreover, the B-LCL derived at 1-2 months post-infection of CLL cells did not express the Leu-1 antigen, but expressed EBV-CS 1 or 4 defined antigens. In the prolymphocytic leukemia, 64% of the cells showed EBNA positivity on day 7 and giant cells with huge round or multiple nuclei appeared which were EBNA-positive. CLL and prolymphocytic leukemia cells can be infected as demonstrated by EBNA-positivity. This infection does not lead to immediate transformation, but evokes lymphoblast and multinucleated giant cell production prior to the death of cells. PMID:3512923

Tatsumi, E; Harada, S; Bechtold, T; Lipscomb, H; Davis, J; Kuszynski, C; Volsky, D J; Han, T; Armitage, J; Purtilo, D T

1986-01-01

287

Therapeutic antagonists of microRNAs deplete leukemia-initiating cell activity  

PubMed Central

Acute myelogenous leukemia (AML) subtypes that result from oncogenic activation of homeobox (HOX) transcription factors are associated with poor prognosis. The HOXA9 transcription activator and growth factor independent 1 (GFI1) transcriptional repressor compete for occupancy at DNA-binding sites for the regulation of common target genes. We exploited this HOXA9 versus GFI1 antagonism to identify the genes encoding microRNA-21 and microRNA-196b as transcriptional targets of HOX-based leukemia oncoproteins. Therapeutic inhibition of microRNA-21 and microRNA-196b inhibited in vitro leukemic colony forming activity and depleted in vivo leukemia-initiating cell activity of HOX-based leukemias, which led to leukemia-free survival in a murine AML model and delayed disease onset in xenograft models. These data establish microRNA as functional effectors of endogenous HOXA9 and HOX-based leukemia oncoproteins, provide a concise in vivo platform to test RNA therapeutics, and suggest therapeutic value for microRNA antagonists in AML. PMID:24334453

Velu, Chinavenmeni S.; Chaubey, Aditya; Phelan, James D.; Horman, Shane R.; Wunderlich, Mark; Guzman, Monica L.; Jegga, Anil G.; Zeleznik-Le, Nancy J.; Chen, Jianjun; Mulloy, James C.; Cancelas, Jose A.; Jordan, Craig T.; Aronow, Bruce J.; Marcucci, Guido; Bhat, Balkrishen; Gebelein, Brian; Grimes, H. Leighton

2013-01-01

288

Histone deacetylase inhibitor treatment downregulates VLA-4 adhesion in hematopoietic stem cells and acute myeloid leukemia blast cells.  

PubMed

The alpha4beta1 integrin very late activation antigen-4 (VLA-4) is an alpha4 (CD49d)/beta1 (CD29) heterodimer. It plays a key role in the adhesion of both hematopoietic progenitor cells and leukemic blast cells to bone marrow stromal cells which express the vascular cell adhesion molecule-1 (VCAM-1) or produce fibronectin. VLA-4 expression has been associated with bone-marrow minimal residual disease, which causes relapse after chemotherapy in patients with acute myelogenous leukemia. Conversely, the absence of VLA-4 reduces bone marrow retention of both hematopoietic progenitor and leukemic blast cells. We report on the downregulation of VLA-4/CD49d for various acute myelogenous leukemia cells lines, on primary cells from patients with acute myelogenous leukemia, and on hematopoietic stem cells and peripheral blood mononuclear cells from healthy donors on treatment with the histone deacetylase inhibitors suberoylanilide hydroxamic acid and valproic acid, which is associated with decreased adhesion to mesenchymal stromal cells. These findings suggest that HDAC-inhibitor treatment may on the one hand impair stem cell homing, while on the other it may improve peripheral blood stem cell mobilization and significantly help to reduce minimal residual disease from acute myelogenous leukemia. PMID:18268283

Mahlknecht, Ulrich; Schönbein, Christiane

2008-03-01

289

[Induction of polyploid in hairy roots of Nicotiana tabacum and its plant regeneration].  

PubMed

By genetic transformation with Agrobacterum rhizogenes and artificial chromosome doubling techniques, we studied the induction of hairy roots and their polyploidization, and subsequent plant regeneration and nicotine determination to enhance the content of nicotine in Nicotiana tabacum. The results show that hairy roots could be induced from the basal surface of leaf explants of N. tabacum 8 days after inoculation with Agrobacterium rhizogenes ATCC15834. The percentage of the rooting leaf explants was 100% 15 days after inoculation. The hairy roots could grow rapidly and autonomously on solid or liquid phytohormones-free MS medium. The transformation was confirmed by PCR amplification of rol gene of Ri plasmid and paper electrophoresis of opines from N. tabacum hairy roots. The highest rate of polyploidy induction, more than 64.71%, was obtained after treatment of hairy roots with 0.1% colchicine for 36 h. The optimum medium for plant regeneration from polyploid hairy roots was MS+2.0 mg/L 6-BA +0.2 mg/L NAA. Compared with the control diploid plants, the hairy roots-regenerated plants had weak apical dominance, more axillary buds and more narrow leaves; whereas the polyploid hairy root-regenerated plants had thicker stems, shorter internodes and the colour, width and thickness of leaves were significantly higher than that of the control. Observation of the number of chromosomes in their root tip cells reveals that the obtained polyploid regenerated plants were tetraploidy, with 96 (4n = 96) chromosomes. Pot-grown experiments showed compared to the control, the flowering was delayed by 21 days in diploid hairy roots-regenerated plants and polyploid hairy root-regenerated plants. GC-MS detection shows that the content of nicotine in polyploid plants was about 6.90 and 4.57 times the control and the diploid hairy roots-regenerated plants, respectively. PMID:25195248

Hou, Lili; Shi, Heping; Yu, Wu; Tsang, Po Keung Eric; Chow, Cheuk Fai Stephen

2014-04-01

290

Anti-leukemic properties of deferasirox via apoptosis in murine leukemia cell lines  

PubMed Central

Background Although deferasirox (DFX) is reported to have anti-tumor effects, its anti-leukemic activity remains unclear. We evaluated the effect of DFX treatment on two murine lymphoid leukemia cell lines, and clarified the mechanisms underlying its potential anti-leukemic activity. Methods L1210 and A20 murine lymphoid leukemia cell lines were treated with DFX. Cell viability and apoptosis were evaluated by the 3-(4,5-dimethylthaizol-2-yl)-5-(3-carboxymethylphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and fluorescence-activated cell sorting (FACS) analysis, respectively. Immunoblotting was performed to detect the expression of key apoptotic proteins. Results In dose- and time-dependent manner, DFX decreased viability and increased apoptosis of murine leukemic cells. Fas expression was significantly higher in A20 cells than in L1210 cells at all DFX concentrations tested. Although both cell lines exhibited high caspase 3 and caspase 9 expression, a critical component of the intrinsic mitochondrial apoptotic pathway, expression was greater in L1210 cells. In contrast, caspase 8, a key factor in the extrinsic apoptotic pathway, showed greater expression in A20 cells. Cytochrome c expression was significantly higher in L1210 cells. In both cell lines, co-treatment with ferric chloride and DFX diminished the expression of these intracellular proteins, as compared to DFX treatment alone. Conclusion Treatment with DFX increased caspase-dependent apoptosis in two murine lymphoid leukemia cell lines, with differing apoptotic mechanisms in each cell line.

Jeon, Sol-Rim; Lee, Jae-Wook; Jang, Pil-Sang; Cho, Bin; Jeong, Dae-Chul

2015-01-01

291

The outcome of B-cell receptor signaling in chronic lymphocytic leukemia: proliferation or anergy  

PubMed Central

Biologists and clinicians agree that the B-cell receptor influences the behavior of chronic lymphocytic leukemia, and promising new drugs are aimed at receptor-associated kinases. Engagement of surface immunoglobulin by antigen is a key driver of malignant cells with outcome influenced by the nature of the cell, the level of stimulation and the microenvironment. Analysis of surface immunoglobulin-mediated signaling in the two major disease subsets defined by IGHV mutational status reveals bifurcation of responses toward proliferation or anergy. Mutated chronic lymphocytic leukemia, generally of relatively good prognosis, is mainly, but not exclusively, driven towards anergy in vivo. In contrast, unmutated chronic lymphocytic leukemia shows less evidence for anergy in vivo retaining more responsiveness to surface immunoglobulin M-mediated signaling, possibly explaining increased tumor progression. Expression and function of surface immunoglobulin M in unmutated chronic lymphocytic leukemia appear rather homogeneous, but mutated chronic lymphocytic leukemia exhibits a highly heterogeneous profile that may relate to further variable clinical behavior within this subset. Anergy should increase susceptibility to apoptosis but, in leukemic cells, this may be countered by overexpression of the B-cell lymphoma-2 survival protein. Maintained anergy spreads to chemokines and adhesion molecules, restraining homing and migration. However, anergy is not necessarily completely benign, being able to reverse and regenerate surface immunoglobulin M-mediated responses. A two-pronged attack on proliferative and anti-apoptotic pathways may succeed. Increased understanding of how chronic lymphocytic leukemia cells are driven to anergy or proliferation should reveal predictive biomarkers of progression and of likely response to kinase inhibitors, which could assist therapeutic decisions. PMID:24986876

Packham, Graham; Krysov, Serge; Allen, Alex; Savelyeva, Natalia; Steele, Andrew J.; Forconi, Francesco; Stevenson, Freda K.

2014-01-01

292

Development of chemotactic responsiveness in myeloid precursor cells: studies with a human leukemia cell line.  

PubMed Central

We have studied the events that occur during the development of chemotaxis in HL60, a promyelocytic leukemia cell line that acquires the features of mature neutrophils when exposed to dimethylformamide (DMF). Chemotactic function first appears between 48 and 96 hr of DMF induction and is associated not only with the coincidental development of deformability, spontaneous motility, greatly increased binding of fMet-Leu-Phe, and orientation but also with decreasing cell size and pleomorphism of nuclei. Surface adhesiveness develops earlier (36-48 hr) and is coincident with a 10-fold increase in protein synthesis not seen in other DMF-inducible cell lines. This burst of protein synthesis precedes the expression of chemotactic function. These studies show that the HL60 cell line can provide a useful model for delineating control mechanisms responsible for the development of complex cellular functions present in differentiated myeloid cells in humans. Images PMID:6932042

Fontana, J A; Wright, D G; Schiffman, E; Corcoran, B A; Deisseroth, A B

1980-01-01

293

-Arrestin2 mediates the initiation and progression of myeloid leukemia  

E-print Network

-Arrestin2 mediates the initiation and progression of myeloid leukemia Mark Fereshteha leukemia (CML). These defects are linked to a re- duced frequency, as well as defective self maintenance. chronic myeloid leukemia | leukemia stem cell | hematopoiesis Chronic myelogenous leukemia (CML

294

DC-SIGN Facilitates Fusion of Dendritic Cells with Human T-Cell Leukemia Virus Type 1Infected Cells  

Microsoft Academic Search

Interactions between the oncogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) and dendritic cells (DCs) are poorly characterized. We show here that monocyte-derived DCs form syncytia and are infected upon coculture with HTLV-1-infected lymphocytes. We examined the role of DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a C-type lectin expressed in DCs, in HTLV-1-induced syncy- tium formation. DC-SIGN is known to bind

Pierre-Emmanuel Ceccaldi; Frederic Delebecque; Marie-Christine Prevost; Arnaud Moris; Jean-Pierre Abastado; Antoine Gessain; Olivier Schwartz; Simona Ozden

2006-01-01

295

T cell chronic lymphocytic leukemia with lymphocytes of unusual immunologic phenotype and function.  

PubMed

This report discusses a case of T cell chronic lymphocytic leukemia (T-CLL) in an elderly white man whose lymphocytes expressed a post-thymic phenotype except for the coexpression of T4 and T8 on 80% to 95% of the cells. Because of the uncommon phenotype, in vitro functional assays were performed that showed decreased mitogenic responses but normal helper activity for B cell immunoglobulin secretion and normal suppressor activity of lectin-induced mitogenesis. Morphologic evaluation by both light and electron microscopy and cytochemical staining were consistent with the "knobby" type T-CLL. Adenosine deaminase and terminal deoxynucleotidyl transferase (TdT) levels were low, but the acetylcholinesterase level was normal, which is consistent with the peripheral T cell phenotype. The patient underwent splenectomy, and the spleen cells showed very low levels of T3 and T4 by immunoperoxidase and undetectable levels by immunofluorescence. The morphology of the splenic infiltrate was not significantly different from that in the initial bone marrow. Human T cell leukemia virus (HTLV) antigen and antibody tests were negative. The cells in this leukemia apparently are derived from a transitional stage of maturation between the cortical and medullary thymocyte. A small subset of lymphocytes of identical phenotype to this leukemia has been identified in normal individuals. PMID:3871160

Simpkins, H; Kiprov, D D; Davis, J L; Morand, P; Puri, S; Grahn, E P

1985-01-01

296

Modeling T-cell acute lymphoblastic leukemia induced by the SCL and LMO1 oncogenes.  

PubMed

Deciphering molecular events required for full transformation of normal cells into cancer cells remains a challenge. In T-cell acute lymphoblastic leukemia (T-ALL), the genes encoding the TAL1/SCL and LMO1/2 transcription factors are recurring targets of chromosomal translocations, whereas NOTCH1 is activated in >50% of samples. Here we show that the SCL and LMO1 oncogenes collaborate to expand primitive thymocyte progenitors and inhibit later stages of differentiation. Together with pre-T-cell antigen receptor (pre-TCR) signaling, these oncogenes provide a favorable context for the acquisition of activating Notch1 mutations and the emergence of self-renewing leukemia-initiating cells in T-ALL. All tumor cells harness identical and specific Notch1 mutations and Tcrbeta clonal signature, indicative of clonal dominance and concurring with the observation that Notch1 gain of function confers a selective advantage to SCL-LMO1 transgenic thymocytes. Accordingly, a hyperactive Notch1 allele accelerates leukemia onset induced by SCL-LMO1 and bypasses the requirement for pre-TCR signaling. Finally, the time to leukemia induced by the three transgenes corresponds to the time required for clonal expansion from a single leukemic stem cell, suggesting that SCL, LMO1, and Notch1 gain of function, together with an active pre-TCR, might represent the minimum set of complementing events for the transformation of susceptible thymocytes. PMID:20516195

Tremblay, Mathieu; Tremblay, Cédric S; Herblot, Sabine; Aplan, Peter D; Hébert, Josée; Perreault, Claude; Hoang, Trang

2010-06-01

297

Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias.  

PubMed

T315I(+) Philadelphia chromosome-positive leukemias are inherently resistant to all licensed tyrosine kinase inhibitors, and therapeutic options remain limited. We report the outcome of allogeneic stem cell transplantation in 64 patients with documented BCR-ABL(T315I) mutations. Median follow-up was 52 months from mutation detection and 26 months from transplantation. At transplantation, 51.5% of patients with chronic myeloid leukemia were in the chronic phase and 4.5% were in advanced phases. Median overall survival after transplantation was 10.3 months (range 5.7 months to not reached [ie, still alive]) for those with chronic myeloid leukemia in the blast phase and 7.4 months (range 1.4 months to not reached [ie, still alive]) for those with Philadelphia chromosome-positive acute lymphoblastic leukemia but has not yet been reached for those in the chronic and accelerated phases of chronic myeloid leukemia. The occurrence of chronic GVHD had a positive impact on overall survival (P = .047). Transplant-related mortality rates were low. Multivariate analysis identified only blast phase at transplantation (hazard ratio 3.68, P = .0011) and unrelated stem cell donor (hazard ratio 2.98, P = .011) as unfavorable factors. We conclude that allogeneic stem cell transplantation represents a valuable therapeutic tool for eligible patients with BCR-ABL(T315I) mutation, a tool that may or may not be replaced by third-generation tyrosine kinase inhibitors. PMID:21926354

Nicolini, Franck Emmanuel; Basak, Grzegorz W; Soverini, Simona; Martinelli, Giovanni; Mauro, Michael J; Müller, Martin C; Hochhaus, Andreas; Chuah, Charles; Dufva, Inge H; Rege-Cambrin, Giovanna; Saglio, Giuseppe; Michallet, Mauricette; Labussière, Hélène; Morisset, Stéphane; Hayette, Sandrine; Etienne, Gabriel; Olavarria, Eduardo; Zhou, Wei; Peter, Senaka; Apperley, Jane F; Cortes, Jorge

2011-11-17

298

Natural killer alloeffector responses in haploidentical hemopoietic stem cell transplantation to treat high-risk leukemias.  

PubMed

Natural killer (NK) cells, a major cell type of the innate immunity, express surface receptors that regulate potent effector functions such as cytolytic activity and release of cytokines playing a central role in inflammatory response and immunoregulation. In this contribution, we briefly outline the major steps from the discovery of human leukocyte antigen (HLA)-class I-specific inhibitory receptors in humans to recent successful clinical applications in the cure of high-risk leukemias both in adults and in pediatric patients. A central role is played by 'alloreactive' NK cells originated from donor's CD 34(+) cells in eradicating leukemic cells in the setting of T-cell-depleted haploidentical hemopoietic stem cell transplantation. Because alloreactive NK cells play a central role also in preventing graft rejection and graft-vs-host disease, they may represent an ideal tool to treat patients affected by acute high-risk leukemias. PMID:20002610

Moretta, L; Locatelli, F; Pende, D; Mingari, M C; Moretta, A

2010-02-01

299

A model with competition between the cell lines in leukemia under treatment  

NASA Astrophysics Data System (ADS)

The evolution of leukemia is modeled with a delay differential equation model of four cell populations: two populations (healthy and leukemic) ) of stem-like cells involving a larger category consisting of proliferating stem and progenitor cells with self-renew capacity and two populations (healthy and leukemic) of mature cells, considering the competition of healthy vs. leukemic cell populations and three types of division that a stem-like cell can exhibit: self-renew, asymmetric division and differentiation. In the model it is assumed that the treatment acts on the proliferation rate of the leukemic stem cells and on the apoptosis of stem and mature cells. The emphasis in this model is on establishing relevant parameters for chronic and acute manifestations of leukemia. Stability of equilibria is investigated and sufficient conditions for local asymptotic stability will be given using a Lyapunov-Krasovskii functional.

Halanay, A.; Cândea, D.; R?dulescu, R.

2014-12-01

300

Treatment Option Overview (Adult Acute Myeloid Leukemia)  

MedlinePLUS

... killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected ... kill leukemia cells, stop the leukemia cells from dividing, or help the leukemia cells mature into white ...

301

Acute myeloid leukemia arising from a donor derived premalignant hematopoietic clone: A possible mechanism for the origin of leukemia in donor cells  

PubMed Central

During recent years, it has become increasingly evident that donor leukemia following allogeneic transplant may be more common then realized in the past. We identified five cases of potential donor leukemia cases during past five years. The precise mechanism of the origin of such leukemias, however, remains poorly defined. In this short communication, we report a well documented case of donor-derived de novo acute myeloid leukemia (AML) that developed fourteen years after allogeneic stem cell transplantation for treatment induced AML for his primary malignancy Immunoblastic lymphoma. This case allows us to postulate a possible mechanism of the origin of donor leukemia. The de novo AML clone contained a distinct cytogenetic abnormality, trisomy 11, which was simultaneously detected in preserved peripheral blood obtained at the time of transplantation as well as in the current bone marrow from an otherwise clinically and phenotypically normal donor. The findings from this unique case, provides insight into the process of leukemogenesis, and suggests that the sequence of events leading to leukemogenesis in this patient involved the senescence/apoptosis of normal donor hematopoietic cells due to telomere shortening resulting in the selective proliferation and transformation of this clone with MLL (mixed-lineage leukemia) gene amplification. PMID:24918066

Dickson, Mark A.; Papadopoulos, Esperanza B.; Hedvat, Cyrus V.; Jhanwar, Suresh C.; Brentjens, Renier J.

2014-01-01

302

Neuroimmunological aspects of human T cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis.  

PubMed

Human T cell leukemia virus type 1 (HTLV-1) is a human retrovirus etiologically associated with adult T cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Only approximately 0.25-4 % of infected individuals develop HAM/TSP; the majority of infected individuals remain lifelong asymptomatic carriers. Recent data suggest that immunological aspects of host-virus interactions might play an important role in the development and pathogenesis of HAM/TSP. This review outlines and discusses the current understanding, ongoing developments, and future perspectives of HAM/TSP research. PMID:23943469

Saito, Mineki

2014-04-01

303

Mutation of the NPM1 gene contributes to the development of donor cell-derived acute myeloid leukemia after unrelated cord blood transplantation for acute lymphoblastic leukemia.  

PubMed

Donor cell leukemia (DCL) is a rare but severe complication after allogeneic stem cell transplantation. Its true incidence is unknown because of a lack of correct recognition and reporting, although improvements in molecular analysis of donor-host chimerism are contributing to a better diagnosis of this complication. The mechanisms of leukemogenesis are unclear, and multiple factors can contribute to the development of DCL. In recent years, cord blood has emerged as an alternative source of hematopoietic progenitor cells, and at least 12 cases of DCL have been reported after unrelated cord blood transplantation. We report a new case of DCL after unrelated cord blood transplantation in a 44-year-old woman diagnosed as having acute lymphoblastic leukemia with t(1;19) that developed acute myeloid leukemia with normal karyotype and nucleophosmin (NPM1) mutation in donor cells. To our knowledge, this is the first report of NPM1 mutation contributing to DCL development. PMID:23465275

Rodríguez-Macías, Gabriela; Martínez-Laperche, Carolina; Gayoso, Jorge; Noriega, Víctor; Serrano, David; Balsalobre, Pascual; Muñoz-Martínez, Cristina; Díez-Martín, José L; Buño, Ismael

2013-08-01

304

Resveratrol Induces Extensive Apoptosis by Depolarizing Mitochondrial Membranes and Activating Caspase9 in Acute Lymphoblastic Leukemia Cells1  

Microsoft Academic Search

Resveratrol, a plant antibiotic, has been found to have anticancer activity and was recently reported to induce apoptosis in the myeloid leukemia line HL60 by the CD95-CD95 ligand pathway. However, many acute lymphoblastic leukemias (ALLs), particularly of B-lineage, are re- sistant to CD95-mediated apoptosis. Using leukemia lines derived from patients with pro-B t(4;11), pre-B, and T-cell ALL, we show in

Jan Dorrie; Harald Gerauer; Yvonne Wachter; Susan J. Zunino

2001-01-01

305

Adult T leukemia cells produce a lymphokine that augments interleukin 2 receptor expression.  

PubMed

Human T-cell leukemia virus (HTLV)-infected cell lines derived from adult T-cell leukemia (ATL) express constitutively the receptor for Interleukin-2 (IL-2-R) and the associated antigen (Tac antigen). In contrast, the same antigen is transiently expressed by normal T-cells only after immune stimulation. Recently, it was reported that the constitutively expressed Tac antigen on ATL cells and cell lines was not down-regulated or modulated by anti-Tac antibody. Since the antigen was modulated on normal mitogen- or alloantigen-stimulated T-cells, we postulated that the regulation of IL-2-R may be abnormal on ATL cells; the synthesis of IL-2-R is continuously stimulated in these cells. A unique HTLV/ATLV(-) cell line (YT) derived from a child with acute lymphoblastic leukemia was found to express low levels of Tac antigen that could be enhanced by various stimuli, including conditioned medium (CM) derived from normal lymphocytes, but not by lectins (PHA, Con A). Of particular interest, the exposure of YT cells to CM from ATL cell lines with helper phenotype revealed the presence of factor(s) (ATL-derived factor, ADF) that augmented the synthesis and expression of IL-2-R/Tac antigen on YT cells and promoted YT cell growth. CM from HTLV(-) leukemia cell lines lacked both IL-2-R augmenting activity and a growth promoting activity. Immunoaffinity-purified IL-2 and recombinant gamma interferon also lacked IL-2-R augmenting activity. Moreover, the physicochemical analysis with Fast protein liquid chromatography (FPLC) revealed that ADF was quite different in pI point from the IL-2-R augmenting activity in CM from normal lymphocytes. These results suggested that ADF is a unique product of HTLV(+) cells. The possible relationship between ADF production, HTLV infection, and the abnormal expression of IL-2-R is suggested, and these abnormalities may be advantageous for the leukemogenesis and abnormal growth of ATL. PMID:2978223

Teshigawara, K; Maeda, M; Nishino, K; Nikaido, T; Uchiyama, T; Tsudo, M; Wano, Y; Yodoi, J

1985-01-01

306

Induction of Erythropoietic Colonies in a Human Chronic Myelogenous Leukemia Cell Line  

Microsoft Academic Search

The ability of cells derived from the K562 dine-positive colonies (19.5 ± 1 hO4 cells) cell line to generate erythropoietic colonies formed. while the combination of sodium was studied. The K562 cell line was derived butyrate plus erythropoietin exerted a from a patient with chronic myelogenous synergistic effect on erythropoietic colony leukemia 8 yr ago by Lozzio and Lozzio. formation

Ronald Hoffman; Mary Jo Murnane; Edward J. Benz; Rainer Prohaska; Victoria Floyd; Nicholas Dainiak; Bernard G. Forget; Heinz Furthmayr

1979-01-01

307

Natural killer cell neoplasms: a distinctive group of highly aggressive lymphomas\\/leukemias  

Microsoft Academic Search

Natural killer (NK) cell neoplasms, which include extranodal NK\\/T-cell lymphoma (nasal and extranasal) and aggressive NK cell leukemia, are generally rare, but they are more common in people of Oriental, Mexican and South American descent. These neoplasms are highly aggressive, and show a strong association with Epstein-Barr virus. Extranodal NK\\/T-cell lymphoma most commonly affects the nasal cavity and other mucosal

Michael M. C Cheung; John K. C Chan; Kit-Fai Wong

2003-01-01

308

Cytoplasmic signaling involved in sonoporation-induced apoptosis and mitosis repression of myeloid leukemia cells  

Microsoft Academic Search

Sonoporation is known to be a transient phenomenon that may disrupt the homeostasis of living cells. In this work, we showed that sonoporation may bear time-lapse impact on cellular viability through up-regulation of cytoplasmic signaling proteins related to apoptosis and cell-cycle arrest. Our experiments were done on HL-60 leukemia cells (10 6 cells\\/ml), and sonoporation was induced via the use

Wenjing Zhong; Wai-Hung Sit; Jennifer M. F. Wan; Alfred C. H. Yu

2010-01-01

309

Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia  

ClinicalTrials.gov

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

2013-10-29

310

Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia  

PubMed Central

B-cell acute lymphoblastic leukemia is the most common type of pediatric leukemia. Despite improved remission rates, current treatment regimens for pediatric B-cell acute lymphoblastic leukemia are often associated with adverse effects and central nervous system relapse, necessitating more effective and safer agents. Bafilomycin A1 is an inhibitor of vacuolar H+-ATPase that is frequently used at high concentration to block late-phase autophagy. Here, we show that bafilomycin A1 at a low concentration (1 nM) effectively and specifically inhibited and killed pediatric B-cell acute lymphoblastic leukemia cells. It targeted both early and late stages of the autophagy pathway by activating mammalian target of rapamycin signaling and by disassociating the Beclin 1-Vps34 complex, as well as by inhibiting the formation of autolysosomes, all of which attenuated functional autophagy. Bafilomycin A1 also targeted mitochondria and induced caspase-independent apoptosis by inducing the translocation of apoptosis-inducing factor from mitochondria to the nucleus. Moreover, bafilomycin A1 induced the binding of Beclin 1 to Bcl-2, which further inhibited autophagy and promoted apoptotic cell death. In primary cells from pediatric patients with B-cell acute lymphoblastic leukemia and a xenograft model, bafilomycin A1 specifically targeted leukemia cells while sparing normal cells. An in vivo mouse toxicity assay confirmed that bafilomycin A1 is safe. Our data thus suggest that bafilomycin A1 is a promising candidate drug for the treatment of pediatric B-cell acute lymphoblastic leukemia. PMID:25512644

Yuan, Na; Song, Lin; Zhang, Suping; Lin, Weiwei; Cao, Yan; Xu, Fei; Fang, Yixuan; Wang, Zhen; Zhang, Han; Li, Xin; Wang, Zhijian; Cai, Jinyang; Wang, Jian; Zhang, Yi; Mao, Xinliang; Zhao, Wenli; Hu, Shaoyan; Chen, Suning; Wang, Jianrong

2015-01-01

311

Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia.  

PubMed

B-cell acute lymphoblastic leukemia is the most common type of pediatric leukemia. Despite improved remission rates, current treatment regimens for pediatric B-cell acute lymphoblastic leukemia are often associated with adverse effects and central nervous system relapse, necessitating more effective and safer agents. Bafilomycin A1 is an inhibitor of vacuolar H(+)-ATPase that is frequently used at high concentration to block late-phase autophagy. Here, we show that bafilomycin A1 at a low concentration (1 nM) effectively and specifically inhibited and killed pediatric B-cell acute lymphoblastic leukemia cells. It targeted both early and late stages of the autophagy pathway by activating mammalian target of rapamycin signaling and by disassociating the Beclin 1-Vps34 complex, as well as by inhibiting the formation of autolysosomes, all of which attenuated functional autophagy. Bafilomycin A1 also targeted mitochondria and induced caspase-independent apoptosis by inducing the translocation of apoptosis-inducing factor from mitochondria to the nucleus. Moreover, bafilomycin A1 induced the binding of Beclin 1 to Bcl-2, which further inhibited autophagy and promoted apoptotic cell death. In primary cells from pediatric patients with B-cell acute lymphoblastic leukemia and a xenograft model, bafilomycin A1 specifically targeted leukemia cells while sparing normal cells. An in vivo mouse toxicity assay confirmed that bafilomycin A1 is safe. Our data thus suggest that bafilomycin A1 is a promising candidate drug for the treatment of pediatric B-cell acute lymphoblastic leukemia. PMID:25512644

Yuan, Na; Song, Lin; Zhang, Suping; Lin, Weiwei; Cao, Yan; Xu, Fei; Fang, Yixuan; Wang, Zhen; Zhang, Han; Li, Xin; Wang, Zhijian; Cai, Jinyang; Wang, Jian; Zhang, Yi; Mao, Xinliang; Zhao, Wenli; Hu, Shaoyan; Chen, Suning; Wang, Jianrong

2015-03-01

312

Lmo2 induces hematopoietic stem cell like features in T-cell progenitor cells prior to leukemia  

PubMed Central

LIM domain Only 2 (Lmo2) is frequently deregulated in sporadic and gene therapy-induced acute T-cell lymphoblastic leukemia (T-ALL) where its overexpression is an important initiating mutational event. In transgenic and retroviral mouse models, Lmo2 expression can be enforced in multiple hematopoietic lineages but leukemia only arises from T cells. These data suggest that Lmo2 confers clonal growth advantage in T-cell progenitors. We analyzed proliferation, differentiation, and cell death in CD2-Lmo2 transgenic thymic progenitor cells to understand the cellular effects of enforced Lmo2 expression. Most impressively, Lmo2 transgenic T-cell progenitor cells were blocked in differentiation, quiescent, and immortalized in vitro on OP9-DL1 stromal cells. These cellular effects were concordant with a transcriptional signature in Lmo2 transgenic T-cell progenitor cells that is also present in hematopoietic stem cells and Early T-cell Precursor ALL. These results are significant in light of the crucial role of Lmo2 in the maintenance of the hematopoietic stem cell. The cellular effects and transcriptional effects have implications for LMO2-dependent leukemogenesis and the treatment of LMO2-induced T-ALL. PMID:23378057

Cleveland, Susan M.; Smith, Stephen; Tripathi, Rati; Mathias, Elizabeth M.; Goodings, Charnise; Elliott, Natalina; Peng, Dunfa; El-Rifai, Wael; Yi, Dajun; Chen, Xi; Li, Liqi; Mullighan, Charles; Downing, James R.; Love, Paul; Davé, Utpal P.

2013-01-01

313

Insights into the stem cells of chronic myeloid leukemia  

Microsoft Academic Search

Chronic myeloid leukemia (CML) has long served as a paradigm for generating new insights into the cellular origin, pathogenesis and improved approaches to treating many types of human cancer. Early studies of the cellular phenotypes and genotypes represented in leukemic populations obtained from CML patients established the concept of an evolving clonal disorder originating in and initially sustained by a

I Sloma; X Jiang; A C Eaves; C J Eaves

2010-01-01

314

Transplantability of human lymphoid cell line, lymphoma, and leukemia in splenectomized and/or irradiated nude mice  

SciTech Connect

The effects of splenectomy and/or whole-body irradiation of nude mice before xenotransplantation of lymphoid cell lines, lymphoma, and leukemia were studied. Transplantation after whole-body irradiation resulted in the increased ''take'' rate of three cultured cell lines (two of T-cell-derived acute lymphocytic leukemia and one of B-cell derived acute lymphocytic leukemia) and in the tumorous growth of Burkitt-derived Raji and spontaneously transformed lymphoblastoid cell lines. With splenectomy plus irradiation as a pretreatment, tumorous growth occurred in four other cell lines which were not transplantable after irradiation only (two cell lines of Epstein-Barr virus-transformed cord blood cells and one each of null acute lymphocytic leukemia and nodular lymphoma-derived cell lines). Direct transplantation of leukemia and lymphoma cells into the pretreated mice was successful in 7 of 24 cases (29%). B-cell-derived diffuse large lymphoid lymphoma was transplantable in three of seven cases (43%). However, lymphoma and leukemia of peripheral T-cell origin was difficult to transplant even with pretreatment, and only one pleomorphic T-cell lymphoma grew to a significant size (2 cm). One tumor each of B-cell-derived diffuse large lymphoid and T-cell diffuse lymphoblastic lymphoma became transplantable.

Watanabe, S.; Shimosato, Y.; Kuroki, M.; Sato, Y.; Nakajima, T.

1980-07-01

315

Risk-Adapted Chemotherapy in Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia  

ClinicalTrials.gov

B-cell Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

2015-03-03

316

Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma  

ClinicalTrials.gov

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

2015-02-02

317

Mimicry of a constitutively active pre–B cell receptor in acute lymphoblastic leukemia cells  

PubMed Central

Pre–B cells undergo apoptosis unless they are rescued by pre–B cell receptor–dependent survival signals. We previously showed that the BCR-ABL1 kinase that is expressed in pre–B lymphoblastic leukemia bypasses selection for pre–B cell receptor–dependent survival signals. Investigating possible interference of BCR-ABL1 with pre–B cell receptor signaling, we found that neither SYK nor SLP65 can be phosphorylated in response to pre–B cell receptor engagement. Instead, Bruton's tyrosine kinase (BTK) is constitutively phosphorylated by BCR-ABL1. Activated BTK is essential for survival signals that otherwise would arise from the pre–B cell receptor, including activation of PLC?1, autonomous Ca2+ signaling, STAT5-phosphorylation, and up-regulation of BCLXL. Inhibition of BTK activity specifically induces apoptosis in BCR-ABL1+ leukemia cells to a similar extent as inhibition of BCR-ABL1 kinase activity itself. However, BCR-ABL1 cannot directly bind to full-length BTK. Instead, BCR-ABL1 induces the expression of a truncated splice variant of BTK that acts as a linker between the two kinases. As opposed to full-length BTK, truncated BTK lacks kinase activity yet can bind to BCR-ABL1 through its SRC-homology domain 3. Acting as a linker, truncated BTK enables BCR-ABL1–dependent activation of full-length BTK, which initiates downstream survival signals and mimics a constitutively active pre–B cell receptor. PMID:15939795

Feldhahn, Niklas; Klein, Florian; Mooster, Jana L.; Hadweh, Paul; Sprangers, Mieke; Wartenberg, Maria; Bekhite, Mohamed M.; Hofmann, Wolf-Karsten; Herzog, Sebastian; Jumaa, Hassan; Rowley, Janet D.; Müschen, Markus

2005-01-01

318

Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant  

ClinicalTrials.gov

Hematopoietic/Lymphoid Cancer; Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Aplastic Anemia; Atypical Chronic Myeloid Leukemia, BCR-ABL Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Cytomegalovirus Infection; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Isolated Plasmacytoma of Bone; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Primary Systemic Amyloidosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Splenic Marginal Zone Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lympho

2014-01-02

319

Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma  

ClinicalTrials.gov

B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

2014-11-26

320

Genetically Engineered Lymphocyte Therapy in Treating Patients With B-Cell Leukemia or Lymphoma That is Resistant or Refractory to Chemotherapy  

ClinicalTrials.gov

Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

2013-10-16

321

The organic arsenic derivative GMZ27 induces PML-RAR?-independent apoptosis in myeloid leukemia cells.  

PubMed

Arsenic trioxide (ATO) is an inorganic arsenic derivative that is very effective against acute promyelocytic leukemia. However, organic arsenic derivatives (OAD) have a more favorable toxicity profile than ATO. We herein characterized dipropil-S-glycerol arsenic (GMZ27), a novel OAD. GMZ27 had potent antiproliferative activity against human acute myeloid leukemia (AML) cell lines that was higher than that of ATO. In contrast to ATO, GMZ27 only marginally induced maturation of leukemia cells and had no effect on the cell cycle. The anti-leukemia activity of GMZ27 against AML cells was independent of the presence of the PML-RAR? fusion protein. GMZ27 dissipates mitochondrial transmembrane potential, and induces cleavage of caspase 9 and activation of caspase 3 without altering the expression levels of (BCL-2), BAX and BCL-xl. GMZ27 induces the formation of intracellular superoxide, a reactive oxygen species (ROS) which plays a major role in the antileukemia activity of this OAD. In addition to ROS generation, GMZ27 concomitantly reduces intracellular glutathione which markedly weakens the cellular antioxidant capacity, thus enhancing the detrimental intracellular effects of ROS production. These results indicate that GMZ27 induces apoptosis in AML cells in a PML-RAR?-independent fashion, through the induction of ROS production. This activity provides the rationale for the testing of GMZ27 in patients with AML. PMID:22753750

Cheng, Xiaodong; Quintás-Cardama, Alfonso; Golemovic, Mirna; Zingaro, Ralph; Gao, Ming-Zhang; Freireich, Emil J; Andreeff, Michael; Kantarjian, Hagop M; Verstovsek, Srdan

2012-07-01

322

Analysis of the inhibitory mechanism of D-allose on MOLT-4F leukemia cell proliferation.  

PubMed

D-Allose, the C-3 epimer of D-glucose, is one of the rare sugars found in nature. In the present study, we have elucidated for the first time that various leukemia cell lines have different susceptibility to anti-proliferative activity of D-allose, and that this difference is related to the difference in induction of thioredoxin interacting protein (TXNIP) expression. We examined 5 leukemia cell lines (MOLT-4F, IM-9, HL-60, BALL-1 and Daudi), and found that MOLT-4F (T-cell lymphoblastic leukemia) had the highest susceptibility to D-allose, and that Daudi (Burkitt's lymphoma) had the lowest. D-Allose significantly slowed the cell cycle progression without causing apoptosis of MOLT-4F cells. Intracellular TXNIP expression was specifically and markedly enhanced in MOLT-4F cells by D-allose treatment, and subsequent increase of p27(kip1), a cell cycle inhibitor, was observed. On the other hand, D-allose did not increase TXNIP and p27(kip1) levels at all in Daudi cells. These results indicate that D-allose suppresses MOLT-4F cell proliferation possibly by the inhibition of cell cycle progression via induction of TXNIP expression. PMID:19393559

Hirata, Yuko; Saito, Madoka; Tsukamoto, Ikuko; Yamaguchi, Fuminori; Sui, Li; Kamitori, Kazuyo; Dong, Youyi; Uehara, Eisuke; Konishi, Ryoji; Janjua, Najma; Tokuda, Masaaki

2009-05-01

323

Hypercalcemia associated with adult T-cell leukemia/lymphoma (ATL).  

PubMed Central

Hypercalcemia is a frequent manifestation of human T-cell lymphotrophic virus type I (HTLV-I)-associated adult T-cell leukemia/lymphoma (ATL). Human T-cell lymphotrophic virus type I infection is endemic in the Caribbean, Japan, Melanesia, and Africa. This article presents two cases of ATL to increase awareness of the disease by primary care physicians. The management of hypercalcemia is discussed. PMID:7473848

Peter, S. A.; Cervantes, J. F.

1995-01-01

324

Deciphering the Evolution of Leukemia-Initiating Cells | Physical Sciences in Oncology  

Cancer.gov

Cancer is a genetic disease, and a major focus in cancer research today is to tease out the details of how cancer cells evolve from a normal cell. Now, an international team of investigators has found that defective genes and the individual leukemia cells that carry them are organized in a more complex way than previously thought. These findings, which were published in the journal Nature, challenge the conventional scientific view that cancer progresses as a linear series of genetic events.

325

Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia  

Microsoft Academic Search

Human T cell leukemias can arise from oncogenes activated by specific chromosomal translocations involving the T cell receptor genes. Here we show that five different T cell oncogenes (HOX11, TAL1, LYL1, LMO1, and LMO2) are often aberrantly expressed in the absence of chromosomal abnormalities. Using oligonucleotide microarrays, we identified several gene expression signatures that were indicative of leukemic arrest at

Adolfo A. Ferrando; Donna S. Neuberg; Jane Staunton; Mignon L. Loh; Christine Huard; Susana C. Raimondi; Fred G. Behm; Ching-Hon Pui; James R. Downing; D. Gary Gilliland; Eric S. Lander; Todd R. Golub; A. Thomas Look

2002-01-01

326

Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation  

Microsoft Academic Search

We investigated the apoptosis gene expression profile of chronic lymphocytic leukemia (CLL) cells in relation to (1) normal peripheral and tonsillar B-cell subsets, (2) IgVH mutation status, and (3) effects of cytotoxic drugs. In accord with their noncycling, antiapoptotic status in vivo, CLL cells displayed high constitutive expression of Bcl-2 and Flip mRNA, while Survivin, Bid and Bik were absent.

W. J. M. Mackus; A. P. Kater; A. Grummels; L. M. Evers; B. Hooijbrink; M. H. H. Kramer; J E Castro; T. J. Kipps; R A W van Lier; M H J van Oers; E. F. Eldering; E Eldering

2005-01-01

327

Systemic mastocytosis in a patient with ovarian germ cell carcinoma and mast cell leukemia  

SciTech Connect

We report a 12-year-old female with a history of mixed germ cell carcinoma of the right ovary who developed a generalized skin rash after oophorectomy and chemotherapy. She also presented with periodic episodes of flushing, anemia, tachycardia, shortness of breath, high fever, hepatosplenomegaly, nausea, abdominal cramping with diarrhea, and a papuloerythematous skin rash. There was no evidence of secondary carcinoma. Skin biopsy revealed nonspecific inflammatory cells with negative staining for mast cells. Peripheral blood smear showed an increased number of mast cells, thrombocytopenia and normal white cells count. Bone marrow showed hypercellularity with 38% of the nucleated cells being mast cells. Bone marrow chromosome analysis revealed hyperdiploidy in 30% of the cells: 58-64,XX, +1, +2, +5, +6, +7, +8, +14, +16, +18, +19, +19, +20, +21, +22. She expired two months after the occurrence of systemic mastocytosis. Systemic mastocytosis has been reported in association with hematopoietic disorders and with germ cell tumors. The association between mediastinal germ cell tumors and hematological malignancies has also been observed. To our knowledge, combination of most cell leukemia, systemic mastocytosis, and ovarian germ cell carcinoma has not been observed. It is know that mutations at the locus of either proto-oncogene c-kit receptor or its ligand, mast/stem cell factor (SCF) may impair the development of three stem cell populations: hematopoietic stem cells, germ cells and melanoblasts. There have been also extensive investigations on the expression and modulation of the SCF/c-kit interaction in various malignancies. Further molecular studies in patients with germ cell tumor/hematopoietic malignancy syndrome are required to delineate underlying mechanisms.

Sun, G.; Hajianpour, M.J.; Hajianpour, A.K. [Alfigen/The Genetics Institute, Pasadena, CA (United States)] [and others

1994-09-01

328

Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines  

Microsoft Academic Search

In this study, we examined a large number of patients to clarify the distribution and frequency of a recently described FLT3 tandem duplication among hematopoietic malignancies, including 112 acute myelocytic leukemia (AML), 55 acute lymphoblastic leukemia (ALL), 37 myelodysplastic syndrome (MDS), 20 chronic myelogenous leukemia (CML), 30 non-Hodgkin’s lymphoma (NHL), 14 adult T cell leukemia, 15 chronic lymphocytic leukemia (CLL)

S Yokota; H Kiyoi; M Nakao; T Iwai; S Misawa; T Okuda; Y Sonoda; T Abe; K Kahsima; Y Matsuo; T Naoe

1997-01-01

329

Cold Spring Harbor's first comprehensive DNA study of mast cell leukemia uncovers clues that could improve therapy:  

Cancer.gov

Cancer researchers at Cold Spring Harbor Laboratory have carried out the first comprehensive study of the changes seen in the DNA of a patient with mast cell leukemia, an extremely aggressive subtype of acute myeloid leukemia with a very poor prognosis.

330

The Role of LMO2 in Development and in T Cell Leukemia After Chromosomal Translocation or Retroviral Insertion  

Microsoft Academic Search

Chromosomal translocations are primary events in the development of leukemias, representing at least one genetic feature of the putative cancer stem cell. Studies of genes influenced by chromosomal translocations have yielded a vast amount of information about how cancer is initiated and maintained. In particular, acute leukemias have demonstrated that chromosomal translocations often involve transcription regulators that function by interacting

Chang-Hoon Nam; Terence H. Rabbitts

2006-01-01

331

A novel crosstalk between calcium/calmodulin kinases II and IV regulates cell proliferation in myeloid leukemia cells.  

PubMed

CaMKs link transient increases in intracellular Ca(2+) with biological processes. In myeloid leukemia cells, CaMKII, activated by the bcr-abl oncogene, promotes cell proliferation. Inhibition of CaMKII activity restricts cell proliferation, and correlates with growth arrest and differentiation. The mechanism by which the inhibition of CaMKII results in growth arrest and differentiation in myeloid leukemia cells is still unknown. We report that inhibition of CaMKII activity results in an upregulation of CaMKIV mRNA and protein in leukemia cell lines. Conversely, expression of CaMKIV inhibits autophosphorylation and activation of CaMKII, and elicits G0/G1cell cycle arrest,impairing cell proliferation. Furthermore, U937 cells expressing CaMKIV show elevated levels of Cdk inhibitors p27(kip1) and p16(ink4a) and reduced levels of cyclins A, B1 and D1. These findings were also confirmed in the K562 leukemic cell line. The relationship between CaMKII and CaMKIV is also observed in primary acute myeloid leukemia (AML) cells, and it correlates with their immunophenotypic profile. Indeed, immature MO/M1 AML showed increased CaMKIV expression and decreased pCaMKII, whereas highly differentiated M4/M5 AML showed decreased CaMKIV expression and increased pCaMKII levels. Our data reveal a novel cross-talk between CaMKII and CaMKIV and suggest that CaMKII suppresses the expression of CaMKIV to promote leukemia cell proliferation. PMID:25446257

Monaco, Sara; Rusciano, Maria Rosaria; Maione, Angela S; Soprano, Maria; Gomathinayagam, Rohini; Todd, Lance R; Campiglia, Pietro; Salzano, Salvatore; Pastore, Lucio; Leggiero, Eleonora; Wilkerson, Donald C; Rocco, Monia; Selleri, Carmine; Iaccarino, Guido; Sankar, Uma; Illario, Maddalena

2015-02-01

332

Oncornavirus-Like Particles from Cultured Bone Marrow Cells Preceding Leukemia and Malignant Histiocytosis  

Microsoft Academic Search

Particles with the density and enzymatic activity characteristic of known oncornavirus have been previously described in bone marrow cells from patients with leukemia in relapse and in remission. We have confirmed these findings and studied two patients in whom preleukemia was among the diagnostic considerations. Following cultivation of bone marrow from these patients for 1 week in conditioned media with

Gerald J. Vosika; William Krivit; Jon M. Gerrard; Peter F. Coccia; Mark E. Nesbit; Jacqueline J. Coalson; B. J. Kennedy

1975-01-01

333

Red cell antigen loss in a patient with chronic myeloid leukemia: A case of ABO discrepancy.  

PubMed

Change in ABO antigen expression on the surface of neoplastic cells have been seen for a variety of tumor types. This phenomenon has been linked with myeloid neoplasms as well but is reported infrequently. Here, we report a rare cause of ABO discrepancy in an elderly female having chronic myeloid leukemia. PMID:25481430

Shafiq, Maria; Karim, Farheen

2015-02-01

334

NYU study discovers new culprit in T-cell acute lymphoblastic leukemia:  

Cancer.gov

A new study published in the journal Nature Medicine by NYU Cancer Institute researchers, shows how the cancer causing gene Notch, in combination with a mutated Polycomb Repressive Complex 2 (PRC2) protein complex, work together to cause T- cell acute lymphoblastic leukemia (T-ALL).

335

Penn researchers find genetically modified T cells cause sustained remissions in patients with chronic lymphocytic leukemia:  

Cancer.gov

Researchers from the University of Pennsylvania's Abramson Cancer Center and Perelman School of Medicine have shown sustained remissions of up to a year among a small group of advanced chronic lymphocytic leukemia (CLL) patients treated with genetically engineered versions of their own T cells.

336

Allogeneic Hematopoietic Cell Transplantation for Adult Patients with Acute Leukemia: The Role of Meta-Analyses  

Microsoft Academic Search

In spite of decades of research in the field of allogeneic hematopoietic cell transplantation for the treatment of acute leukemia, controversies regarding the role of transplant still exist. These stem not only from contradictory results of different studies, but also from differences in the design and the strength of evidence of the various trials. Meta-analysis is considered the highest level

Ron Ram; Anat Gafter-Gvili; Ofer Shpilberg; Pia Raanani

2011-01-01

337

Crystal structure of human T cell leukemia virus protease, a novel target for anticancer drug design  

E-print Network

responsible for the resistance of HTLV-1 PR to anti-HIV drugs are identified. We expect that the knowledge accumulated during the development of anti-HIV drugs, particularly in overcoming drug resistance, will helpCrystal structure of human T cell leukemia virus protease, a novel target for anticancer drug

338

Investigating human leukemogenesis: from cell lines to in vivo models of human leukemia  

Microsoft Academic Search

The hematopoietic system produces appropriate levels of blood cells over an individual's lifetime through a careful balance of differentiation, proliferation and self-renewal. The acquisition of genetic and epigenetic alterations leads to deregulation of these processes and the development of acute leukemias. A prerequisite to targeted therapies directed against these malignancies is a thorough understanding of the processes that subvert the

J A Kennedy; F Barabé

2008-01-01

339

Host Cell Cathepsins Potentiate Moloney Murine Leukemia Virus Infection  

Microsoft Academic Search

The roles of cellular proteases in Moloney murine leukemia virus (MLV) infection were investigated using MLV particles pseudotyped with vesicular stomatitis virus (VSV) G glycoprotein as a control for effects on core MLV particles versus effects specific to Moloney MLV envelope protein (Env). The broad-spectrum inhibitors cathepsin inhibitor III and E-64d gave comparable dose-dependent inhibition of Moloney MLV Env and

Pankaj Kumar; Deepa Nachagari; Carolyn Fields; John Franks; Lorraine M. Albritton

2007-01-01

340

Phosphatidylserine index as a marker of the procoagulant phenotype of acute myelogenous leukemia cells  

NASA Astrophysics Data System (ADS)

Patients with acute myelogenous leukemia (AML) are at risk for thrombotic complications. Risk to develop thrombosis is closely tied to leukemia subtype, and studies have shown an association between leukocytosis and thrombosis in AML M3. We evaluated the relative roles of cell count and the surface expression of tissue factor (TF) and phosphatidylserine (PS) in the procoagulant phenotype of AML cell lines. The TF-positive AML M3 cell lines, NB4 and HL60, and AML M2 cell line, AML14, exhibited both extrinsic tenase and prothrombinase activity in a purified system and promoted experimental thrombus formation. In contrast, the TF-negative AML cell line, HEL, exhibited only prothrombinase activity and did not affect the rate of occlusive thrombus formation. In plasma, NB4, HL60 and AML14 shortened clotting times in a cell-count, PS- and TF-dependent manner. Exposure of cultured NB4, HL60, and AML14 cells to the chemotherapeutic agent daunorubicin increased their extrinsic tenase activity and PS expression. Clot initiation time inversely correlated with logarithm of PS index, defined as the product of multiplying leukocyte count with cell surface PS exposure. We propose that leukemia cell PS index may serve as a biomarker for procoagulant activity.

Tormoen, Garth W.; Recht, Olivia; Gruber, András; Levine, Ross L.; McCarty, Owen J. T.

2013-10-01

341

Antioxidant activity of Vaccinium stamineum: exhibition of anticancer capability in human lung and leukemia cells.  

PubMed

Fruit of deerberry [Vaccinium stamineum L.] were evaluated for their antioxidant capacity and anticancer properties in JB6 P (+) mouse epidermal cells, human lung and leukemia cells. Deerberries contain potent free radical scavenging activities. Pretreatment of JB6 P (+) mouse epidermal cells with deerberry fruit extracts produced an inhibition on the activation of activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) induced by either 12- O-tetradecanoylphorbol 13-acetate (TPA) or ultraviolet-B (UVB). Deerberry fruit extracts also blocked TPA- or UVB-induced phosphorylation of ERKs and MEK 1/2, two upstream regulators of AP-1 and inhibited proliferation of human leukemia HL-60 cancer cells and human lung epithelial cancer A549 cells and induced apoptosis of HL-60 cells. These results suggest that the inhibition of TPA- or UVB-induced AP-1 and NF-kappaB activity, inhibition of HL-60 cells and cancer A549 cells proliferation and induction of apoptotic in human leukemia HL-60 cancer cells may be mediated through the ERKs and MEK 1/2 signal pathway. PMID:17394101

Wang, Shiow Y; Feng, Rentian; Bowman, Linda; Lu, Yongju; Ballington, James R; Ding, Min

2007-05-01

342

Molecular Targeting of the Oncoprotein PLK1 in Pediatric Acute Myeloid Leukemia: RO3280, a Novel PLK1 Inhibitor, Induces Apoptosis in Leukemia Cells  

PubMed Central

Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor; however its therapeutic effects in leukemia treatment are still unknown. We found that the PLK1 protein was highly expressed in leukemia cell lines as well as 73.3% (11/15) of pediatric acute myeloid leukemia (AML) samples. PLK1 mRNA expression was significantly higher in AML samples compared with control samples (82.95 ± 110.28 vs. 6.36 ± 6.35; p < 0.001). Kaplan-Meier survival analysis revealed that shorter survival time correlated with high tumor PLK1 expression (p = 0.002). The 50% inhibitory concentration (IC50) of RO3280 for acute leukemia cells was between 74 and 797 nM. The IC50 of RO3280 in primary acute lymphocytic leukemia (ALL) and AML cells was between 35.49 and 110.76 nM and 52.80 and 147.50 nM, respectively. RO3280 induced apoptosis and cell cycle disorder in leukemia cells. RO3280 treatment regulated several apoptosis-associated genes. The regulation of DCC, CDKN1A, BTK, and SOCS2 was verified by western blot. These results provide insights into the potential use of RO3280 for AML therapy; however, the underlying mechanisms remain to be determined. PMID:25574601

Wang, Na-Na; Li, Zhi-Heng; Zhao, He; Tao, Yan-Fang; Xu, Li-Xiao; Lu, Jun; Cao, Lan; Du, Xiao-Juan; Sun, Li-Chao; Zhao, Wen-Li; Xiao, Pei-Fang; Fang, Fang; Su, Guang-Hao; Li, Yan-Hong; Li, Gang; Li, Yi-Ping; Xu, Yun-Yun; Zhou, Hui-Ting; Wu, Yi; Jin, Mei-Fang; Liu, Lin; Ni, Jian; Wang, Jian; Hu, Shao-Yan; Zhu, Xue-Ming; Feng, Xing; Pan, Jian

2015-01-01

343

Molecular targeting of the oncoprotein PLK1 in pediatric acute myeloid leukemia: RO3280, a novel PLK1 inhibitor, induces apoptosis in leukemia cells.  

PubMed

Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor; however its therapeutic effects in leukemia treatment are still unknown. We found that the PLK1 protein was highly expressed in leukemia cell lines as well as 73.3% (11/15) of pediatric acute myeloid leukemia (AML) samples. PLK1 mRNA expression was significantly higher in AML samples compared with control samples (82.95 ± 110.28 vs. 6.36 ± 6.35; p < 0.001). Kaplan-Meier survival analysis revealed that shorter survival time correlated with high tumor PLK1 expression (p = 0.002). The 50% inhibitory concentration (IC50) of RO3280 for acute leukemia cells was between 74 and 797 nM. The IC50 of RO3280 in primary acute lymphocytic leukemia (ALL) and AML cells was between 35.49 and 110.76 nM and 52.80 and 147.50 nM, respectively. RO3280 induced apoptosis and cell cycle disorder in leukemia cells. RO3280 treatment regulated several apoptosis-associated genes. The regulation of DCC, CDKN1A, BTK, and SOCS2 was verified by western blot. These results provide insights into the potential use of RO3280 for AML therapy; however, the underlying mechanisms remain to be determined. PMID:25574601

Wang, Na-Na; Li, Zhi-Heng; Zhao, He; Tao, Yan-Fang; Xu, Li-Xiao; Lu, Jun; Cao, Lan; Du, Xiao-Juan; Sun, Li-Chao; Zhao, Wen-Li; Xiao, Pei-Fang; Fang, Fang; Su, Guang-Hao; Li, Yan-Hong; Li, Gang; Li, Yi-Ping; Xu, Yun-Yun; Zhou, Hui-Ting; Wu, Yi; Jin, Mei-Fang; Liu, Lin; Ni, Jian; Wang, Jian; Hu, Shao-Yan; Zhu, Xue-Ming; Feng, Xing; Pan, Jian

2015-01-01

344

Antitumor screening of Pterodon pubescens terpenic fraction indicates high sensitivity for lymphocytic leukemia cells.  

PubMed

Cancer is the second leading cause of human mortality worldwide. Therefore, the search for new drugs or alternative therapy strategies has been required. Anticancer agents have been developed from plants since the 1950s and natural products still represent an important source of new and promising bioactive molecules. This work describes the cytotoxic effects of SF5 on tumor cells of high prevalence in the world and investigated some mechanisms of its antitumor action. The antitumor screening was performed with human lung carcinoma (A549), human breast (MCF-7) and prostate (PC-3) adenocarcinoma and chronic myeloid and acute lymphocytic leukemia cell lines. The acute lymphocytic leukemia Jurkat cells presented high sensitivity to the cytotoxic effects of SF5 (inhibition of 85-90%), compared with either the chronic myeloid leukemia K562 or solid tumor cell lines (lung, breast and prostate). SF5 arrested the cell cycle in G1 phase, which may be related with the observed downregulation of mRNA expression of c-Myc transcription factor at 24 h and 36 h. SF5 treatment induced cytochrome c release from mitochondria to cytosol, leading the Jurkat cells into apoptosis, which was evidenced by the internucleosomal fragmented DNA and increased number of annexin V-FITC positive cells. The SF5 showed high cytotoxicity for lymphocytic leukemia cells and low or none for solid tumor cells, without toxicity for peripheral mononuclear cells of healthy humans. SF5 altered gene expression, arrested the cell cycle and induced apoptosis via the mitochondrial pathway, similar to traditional antineoplastic chemotherapeutic drugs. PMID:25532277

Martino, Thiago; Pereira, Monica F; Gayer, Carlos R M; Dalmau, Sergio R; Coelho, Marsen G P; Sabino, Kátia C C

2014-11-01

345

Donor Stem Cell Transplant in Treating Patients With High Risk Acute Myeloid Leukemia  

ClinicalTrials.gov

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

2014-09-17

346

Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia Who Have Undergone Stem Cell Transplant  

ClinicalTrials.gov

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

2015-03-02

347

Pterostilbene induces accumulation of autophagic vacuoles followed by cell death in HL60 human leukemia cells.  

PubMed

Pterostilbene, a naturally occurring structural analog of resveratrol, has been reported to exert antiproliferative and proapoptotic effects in various cancer types. Recently, it has been demonstrated to induce both autophagy and apoptosis in human bladder and breast cancer cell lines. The aim of this study was to evaluate the effects of pterostilbene on HL60 human leukemia cells. Cell morphology was examined using confocal and electron microscopy. Cell viability was determined by MTT, neutral red uptake and trypan blue exclusion assays. LC3 processing was studied based on Western blotting and immunofluorescence analyses. Flow cytometry was used to study cell cycle distribution, phosphatidylserine externalization, caspase activation, disruption of mitochondrial membrane potential and intracellular production of reactive oxygen species. DNA degradation was examined by gel electrophoresis. We found that treatment of HL60 cells with pterostilbene at the IC90 concentration resulted in the G0/G1 cell cycle arrest. Pterostilbene induced conversion of cytosolic LC3-I to membrane-bound LC3-II and accumulation of large LC3-positive vacuolar structures. Pterostilbene also led to phosphatidylserine externalization, internucleosomal DNA fragmentation, caspase activation and disruption of mitochondrial membrane potential. Moreover, it did not induce oxidative stress. Our results suggest that pterostilbene induces accumulation of autophagic vacuoles followed by cell death in HL60 cells. PMID:24304568

Siedlecka-Kroplewska, K; Jozwik, A; Boguslawski, W; Wozniak, M; Zauszkiewicz-Pawlak, A; Spodnik, J H; Rychlowski, M; Kmiec, Z

2013-10-01

348

[Aleukemic mast cell leukemia (formerly: "malignant mastocytosis"): an extremely rare form of leukemia. A case report and simultaneously a contribution to revised classification of mastocytosis].  

PubMed

The term mastocytosis denotes a heterogeneous group of rare hematological disorders characterized by abnormal accumulation of mast cells. While cutaneous mastocytosis is relatively frequent mast cell leukemia belongs to the rarest forms of human leukemia. In the following we present the case of an aleukemic mast cell leukemia and shall discuss the revised classification of mastocytosis based on the "Year 2000 Working Conference on Mastocytosis" held in Vienna, Austria. A 48 year-old caucasian man presented with a four-week history of diarrhea, obstipation, vomiting, rash, and mild fever. Clinical inspection revealed a disseminated itching rash and a mild hepatomegaly. Red and white blood cell counts were within the normal range. Levels of the alkaline phosphatase and serum histamine were significantly increased. There was no splenomegaly or lymphadenopathy. Cytologic and histologic investigation of the bone marrow revealed a marked increase in atypical mast cells. Since only a few circulating mast cells could be detected in a cytospin preparation of the blood, the diagnosis of an aleukemic mast cell leukemia was established. About four weeks after the diagnosis had been established, the patient died with signs of a hemorrhagic shock due to a massive gastrointestinal bleeding. Autopsy revealed widespread mast cell infiltration of bone marrow, spleen, liver and lungs, but also a small, deeply penetrating, non-specific duodenal ulcer. In conclusion, despite of presentation with signs of a primary gastrointestinal disorder, the patient was found to suffer from an exceedingly rare aleukemic mast cell leukemia ("malignant mastocytosis") and died after a total duration of the disease of only about three months. PMID:12238313

Horny, Hans-Peter; Krokowski, Manuela; Feller, Alfred C; Hintze, Gerhard; Sotlar, Karl; Valent, Peter

2002-03-28

349

Blood dendritic cells suppress NK cell function and increase the risk of leukemia relapse after hematopoietic cell transplantation.  

PubMed

NK cells play an important role in hematopoietic stem cell transplantation (HCT) and in cross talk with dendritic cells (DCs) to induce primary T cell response against infection. Therefore, we hypothesized that blood DCs should augment NK cell function and reduce the risk of leukemia relapse after HCT. To test this hypothesis, we conducted laboratory and clinical studies in parallel. We found that although, phenotypically, NK cells could induce DC maturation and DCs could in turn increase activating marker expression on NK cells, paradoxically, both BDCA1(+) myeloid DCs and BDCA4(+) plasmacytoid DCs suppressed the function of NK cells. Patients who received an HLA-haploidentical graft containing a larger number of BDCA1(+) DCs or BDCA4(+) DCs had a higher risk of leukemia relapse and poorer survival. Further experiments indicated that the potent inhibition on NK cell cytokine production and cytotoxicity was mediated in part through the secretion of IL-10 by BDCA1(+) DCs and IL-6 by BDCA4(+) DCs. These results have significant implications for future HCT strategies. PMID:20977942

Perez-Martinez, Antonio; Iyengar, Rekha; Gan, Kwan; Chotsampancharoen, Thirachit; Rooney, Barbara; Holladay, Marti; Ramírez, Manuel; Leung, Wing

2011-05-01

350

Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal.  

PubMed

Mast cell leukemia (MCL), the leukemic manifestation of systemic mastocytosis (SM), is characterized by leukemic expansion of immature mast cells (MCs) in the bone marrow (BM) and other internal organs; and a poor prognosis. In a subset of patients, circulating MCs are detectable. A major differential diagnosis to MCL is myelomastocytic leukemia (MML). Although criteria for both MCL and MML have been published, several questions remain concerning terminologies and subvariants. To discuss open issues, the EU/US-consensus group and the European Competence Network on Mastocytosis (ECNM) launched a series of meetings and workshops in 2011-2013. Resulting discussions and outcomes are provided in this article. The group recommends that MML be recognized as a distinct condition defined by mastocytic differentiation in advanced myeloid neoplasms without evidence of SM. The group also proposes that MCL be divided into acute MCL and chronic MCL, based on the presence or absence of C-Findings. In addition, a primary (de novo) form of MCL should be separated from secondary MCL that typically develops in the presence of a known antecedent MC neoplasm, usually aggressive SM (ASM) or MC sarcoma. For MCL, an imminent prephase is also proposed. This prephase represents ASM with rapid progression and 5%-19% MCs in BM smears, which is generally accepted to be of prognostic significance. We recommend that this condition be termed ASM in transformation to MCL (ASM-t). The refined classification of MCL fits within and extends the current WHO classification; and should improve prognostication and patient selection in practice as well as in clinical trials. PMID:24675021

Valent, P; Sotlar, K; Sperr, W R; Escribano, L; Yavuz, S; Reiter, A; George, T I; Kluin-Nelemans, H C; Hermine, O; Butterfield, J H; Hägglund, H; Ustun, C; Hornick, J L; Triggiani, M; Radia, D; Akin, C; Hartmann, K; Gotlib, J; Schwartz, L B; Verstovsek, S; Orfao, A; Metcalfe, D D; Arock, M; Horny, H-P

2014-09-01

351

Membrane transport changes in an adriamycin-resistant murine leukemia cell line and in its sensitive parental cell line  

Microsoft Academic Search

Multidrug resistance in cancer chemotherapy occurs when cells develop resistance towards structurally and functionally unrelated drugs. It is speculated that alteration of some fundamental process(es) in the cells leads to the development of multidrug resistance. The sodium pump activity of murine leukemia cell lines P388\\/S (sensitive) and P388\\/ADR (resistant) was measured and found to be different in the two cell

Ratna Bose; Hing-Yat Peter Lain

1988-01-01

352

Vitamin D3 potentiates the antitumorigenic effects of arsenic trioxide in human leukemia (HL-60) cells  

PubMed Central

Background Arsenic trioxide (ATO) is a novel form of therapy that has been found to aid acute promyelocytic leukemia (APL) patients. Our laboratory has demonstrated that ATO-induced cytotoxicity in human leukemia (HL-60) cells is mediated by oxidative stress. Pro-oxidants have been known to play a role in free radical-mediated oxidative stress. Vitamin D3, (Vit D3) an active metabolite of vitamin D has been reported to inhibit the growth of number neoplasms such as prostate, breast, colorectal, leukemia, and skin cancers. The goal of the present research was to use (HL-60) cells as an in vitro test model to evaluate whether low doses of Vit D3 potentiate the toxicity of ATO and whether this toxic action is mediated via apoptotic mechanisms. Method HL-60 cells were treated either with a pharmacologic dose of ATO alone and with several low doses of Vit D3. Cell survival was determined by MTT assay. Cell apoptosis was measured both by flow cytometry assessment, and DNA laddering assay. Results MTT assay indicated that Vit D3 co-treatment potentiates ATO toxicity in HL-60 cells in a dose dependent manner. A statistically significant and dose-dependent increase (p <0.05) was recorded in annexin V positive cells (apoptotic cells) with increasing doses of Vit D3 in ATO-treated cells. This finding was confirmed by the result of DNA laddering assay showing clear evidence of nucleosomal DNA fragmentation in vitamin and ATO co-treated cells. Conclusion The present study indicates that Vit D3 potentiates the antitumor effects of ATO. This potentiation is mediated at least in part, through induction of phosphatidylserine externalization and nucleosomal DNA fragmentation. These findings highlight the potential impact of Vit D3 in promoting the pharmacological effect of ATO, suggesting a possible future role of Vit D3/ATO combination therapy in patients with acute promyelocytic leukemia (APL). PMID:24661615

2014-01-01

353

Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia  

ClinicalTrials.gov

B-Cell Prolymphocytic Leukemia; Plasma Cell Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Non-Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

2015-03-17

354

[Leukemia SH-1 cells purged by ZnPcH(1)-based photodynamic therapy].  

PubMed

The objective of this study was to investigate the effect of a novel Zinc phthalocyanine (ZnPcH(1)) based photodynamic therapy (PDT) on acute monocytic leukemia cell lines SHI-1 and its mechanism, so as to provide theory basis for bone marrow purging in vitro for patients with leukemia. The killing effect of ZnPcH(1)-PDT on SHI-1 cells were assessed by MTT method; the SHI-1 cell death patterns were analyzed by AO/EB fluorescence staining, TdT-mediated dUTP nick end labeling (TUNEL), DNA ploidy analysis, and Annexin V-FITC/PI double staining.Cell mixture was established by integrating SHI-1 cells with normal bone marrow MNC (by 1:100-1:10 000). Purging effect of ZnPcH(1)-PDT against SHI-1 mixed into normal MNC was assessed by analyzing the expression of fusion gene MLL/AF6 mRNA using nested RT-PCR. The results showed that ZnPcH(1)-PDT could effectively inhibit SHI-1 cell proliferation in dose-dependent manner, and ZnPcH(1)-PDT could induce cell apoptosis in time-dependent manner. 0.5 µmol/L ZnPcH(1)-PDT could completely photoinactivated kill SHI-1 cells in the simulated remission bone marrow. It concluded that ZnPcH(1)-PDT may be a effective and convenient promising purging technique for leukemia. PMID:22931639

Lin, Xiao-Lan; Huang, Hui-Fang; Chen, Wan-Zi

2012-08-01

355

Recognition of adult and pediatric acute lymphoblastic leukemia blasts by natural killer cells.  

PubMed

In this study, we aimed to investigate the pathways of recognition of acute lymphoblastic leukemia blasts by natural killer cells and to verify whether differences in natural killer cell activating receptor ligand expression among groups defined by age of patients, or presence of cytogenetic/molecular aberrations correlate with the susceptibility to recognition and killing. We analyzed 103 newly diagnosed acute lymphoblastic leukemia patients: 46 adults and 57 children. Pediatric blasts showed a significantly higher expression of Nec-2 (P=0.03), ULBP-1 (P=0.01) and ULBP-3 (P=0.04) compared to adult cells. The differential expression of these ligands between adults and children was confined to B-lineage acute lymphoblastic leukemia with no known molecular alterations. Within molecularly defined subgroups of patients, a high surface expression of NKG2D and DNAM1 ligands was found on BCR-ABL(+) blasts, regardless of patient age. Accordingly, BCR-ABL(+) blasts proved to be significantly more susceptible to natural killer-dependent lysis than B-lineage blasts without molecular aberrations (P=0.03). Cytotoxic tests performed in the presence of neutralizing antibodies indicated a pathway of acute lymphoblastic leukemia cell recognition in the setting of the Nec-2/DNAM-1 interaction. These data provide a biological explanation of the different roles played by alloreactive natural killer cells in pediatric versus adult acute lymphoblastic leukemia and suggest that new natural killer-based strategies targeting specific subgroups of patients, particularly those BCR-ABL(+), are worth pursuing further. PMID:24658822

Torelli, Giovanni F; Peragine, Nadia; Raponi, Sara; Pagliara, Daria; De Propris, Maria S; Vitale, Antonella; Bertaina, Alice; Barberi, Walter; Moretta, Lorenzo; Basso, Giuseppe; Santoni, Angela; Guarini, Anna; Locatelli, Franco; Foà, Robin

2014-07-01

356

Recognition of adult and pediatric acute lymphoblastic leukemia blasts by natural killer cells  

PubMed Central

In this study, we aimed to investigate the pathways of recognition of acute lymphoblastic leukemia blasts by natural killer cells and to verify whether differences in natural killer cell activating receptor ligand expression among groups defined by age of patients, or presence of cytogenetic/molecular aberrations correlate with the susceptibility to recognition and killing. We analyzed 103 newly diagnosed acute lymphoblastic leukemia patients: 46 adults and 57 children. Pediatric blasts showed a significantly higher expression of Nec-2 (P=0.03), ULBP-1 (P=0.01) and ULBP-3 (P=0.04) compared to adult cells. The differential expression of these ligands between adults and children was confined to B-lineage acute lymphoblastic leukemia with no known molecular alterations. Within molecularly defined subgroups of patients, a high surface expression of NKG2D and DNAM1 ligands was found on BCR-ABL+ blasts, regardless of patient age. Accordingly, BCR-ABL+ blasts proved to be significantly more susceptible to natural killer-dependent lysis than B-lineage blasts without molecular aberrations (P=0.03). Cytotoxic tests performed in the presence of neutralizing antibodies indicated a pathway of acute lymphoblastic leukemia cell recognition in the setting of the Nec-2/DNAM-1 interaction. These data provide a biological explanation of the different roles played by alloreactive natural killer cells in pediatric versus adult acute lymphoblastic leukemia and suggest that new natural killer-based strategies targeting specific subgroups of patients, particularly those BCR-ABL+, are worth pursuing further. PMID:24658822

Torelli, Giovanni F.; Peragine, Nadia; Raponi, Sara; Pagliara, Daria; De Propris, Maria S.; Vitale, Antonella; Bertaina, Alice; Barberi, Walter; Moretta, Lorenzo; Basso, Giuseppe; Santoni, Angela; Guarini, Anna; Locatelli, Franco; Foà, Robin

2014-01-01

357

Acute Lymphocytic Leukemia  

MedlinePLUS

... hard for blood to do its work. In acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, there are too ... of white blood cells called lymphocytes or lymphoblasts. ALL is the most common type of cancer in ...

358

Leukemia cell-targeted STAT3 silencing and TLR9 triggering generate systemic antitumor immunity.  

PubMed

Signal transducer and activator of transcription 3 (STAT3) is an oncogene and immune checkpoint commonly activated in cancer cells and in tumor-associated immune cells. We previously developed an immunostimulatory strategy based on targeted Stat3 silencing in Toll-like receptor 9 (TLR9)-positive hematopoietic cells using CpG-small interfering RNA (siRNA) conjugates. Here, we assessed the therapeutic effect of systemic STAT3 blocking/TLR9 triggering in disseminated acute myeloid leukemia (AML). We used mouse Cbfb-MYH11/Mpl-induced leukemia model, which mimics human inv(16) AML. Our results demonstrate that intravenously delivered CpG-Stat3 siRNA, but not control oligonucleotides, can eradicate established AML and impair leukemia-initiating potential. These antitumor effects require host's effector T cells but not TLR9-positive antigen-presenting cells. Instead, CpG-Stat3 siRNA has direct immunogenic effect on AML cells in vivo upregulating major histocompatibility complex class-II, costimulatory and proinflammatory mediators, such as interleukin-12, while downregulating coinhibitory PD-L1 molecule. Systemic injections of CpG-Stat3 siRNA generate potent tumor antigen-specific immune responses, increase the ratio of tumor-infiltrating CD8(+) T cells to regulatory T cells in various organs, and result in CD8(+) T-cell-dependent regression of leukemia. Our findings underscore the potential of using targeted STAT3 inhibition/TLR9 triggering to break tumor tolerance and induce immunity against AML and potentially other TLR9-positive blood cancers. PMID:24169824

Hossain, Dewan Md Sakib; Dos Santos, Cedric; Zhang, Qifang; Kozlowska, Anna; Liu, Hongjun; Gao, Chan; Moreira, Dayson; Swiderski, Piotr; Jozwiak, Agnieszka; Kline, Justin; Forman, Stephen; Bhatia, Ravi; Kuo, Ya-Huei; Kortylewski, Marcin

2014-01-01

359

Leukemia cell–targeted STAT3 silencing and TLR9 triggering generate systemic antitumor immunity  

PubMed Central

Signal transducer and activator of transcription 3 (STAT3) is an oncogene and immune checkpoint commonly activated in cancer cells and in tumor-associated immune cells. We previously developed an immunostimulatory strategy based on targeted Stat3 silencing in Toll-like receptor 9 (TLR9)-positive hematopoietic cells using CpG-small interfering RNA (siRNA) conjugates. Here, we assessed the therapeutic effect of systemic STAT3 blocking/TLR9 triggering in disseminated acute myeloid leukemia (AML). We used mouse Cbfb-MYH11/Mpl-induced leukemia model, which mimics human inv(16) AML. Our results demonstrate that intravenously delivered CpG-Stat3 siRNA, but not control oligonucleotides, can eradicate established AML and impair leukemia-initiating potential. These antitumor effects require host’s effector T cells but not TLR9-positive antigen-presenting cells. Instead, CpG-Stat3 siRNA has direct immunogenic effect on AML cells in vivo upregulating major histocompatibility complex class-II, costimulatory and proinflammatory mediators, such as interleukin-12, while downregulating coinhibitory PD-L1 molecule. Systemic injections of CpG-Stat3 siRNA generate potent tumor antigen–specific immune responses, increase the ratio of tumor-infiltrating CD8+ T cells to regulatory T cells in various organs, and result in CD8+ T-cell–dependent regression of leukemia. Our findings underscore the potential of using targeted STAT3 inhibition/TLR9 triggering to break tumor tolerance and induce immunity against AML and potentially other TLR9-positive blood cancers. PMID:24169824

Hossain, Dewan Md Sakib; Dos Santos, Cedric; Zhang, Qifang; Kozlowska, Anna; Liu, Hongjun; Gao, Chan; Moreira, Dayson; Swiderski, Piotr; Jozwiak, Agnieszka; Kline, Justin; Forman, Stephen; Bhatia, Ravi; Kuo, Ya-Huei

2014-01-01

360

Defective Chemokine Production in T-Leukemia Cell Lines and its Possible Functional Role  

PubMed Central

Peripheral blood lymphocytes and T-cell clones produced nanogram quantities of the chemokines RANTES, MIP-l?, MIP-l?, MCP-l, IL-8 and GRO-? as well as the motogenic cytokine HGF. In contrast, various T-leukemia cell lines at different stages of differentiation did not produce the same chemokines/cytokines. In order to study the possible functional importance of the poor chemokine production different T-cell lines were compared with respect to development of motile forms and migration on extracellular matrix components in the absence and presence of various chemokines. RANTES, MIP-1?, MIP-1?, IL-8, GRO-? and lymphotactin did not augment the development of motile forms including the size and appearance of the pseudopodia activity of the T-leukemia cell lines. The T-cell lines migrated spontaneously on/to fibronectin in a Boyden chamber assay system. Chemokines augmented the migration of the T-leukemia cell lines on fibronectin in the Boyden system in a chemotactic fashion with peak responses at 10 to 50 ng/ml. Thus, the production of chemokines is defective, in neoplastic T-lymphocytes. The defective chemokine production does not seem to play any major role for the basic locomotor capacity of the cells but may modulate the responsiveness to exogenous chemokines. PMID:11097202

Ivanoff, Jyrki; Ivanoff, Anna

2000-01-01

361

In Childhood Acute Lymphoblastic Leukemia, Blasts At Different Stages Of Immunophenotypic Maturation Have Stem Cell Properties  

PubMed Central

Summary We examined the leukemic stem cell potential of blasts at different stages of maturation in childhood acute lymphoblastic leukemia. Human leukemic bone marrow was transplanted intrafemorally into NOD/scid mice. Cells sorted using the B precursor differentiation markers CD19, CD20 and CD34 were isolated from patient samples and engrafted mice before serial transplantation into primary or subsequent (up to quaternary) recipients. Surprisingly, blasts representative of all the different maturational stages were able to reconstitute and re-establish the complete leukemic phenotype in vivo. Sorted blast populations mirrored normal B precursor cells with transcription of a number of stage-appropriate genes. These observations have informed a model for leukemia-propagating stem cells in childhood ALL. PMID:18598943

le Viseur, Christoph; Hotfilder, Marc; Bomken, Simon; Wilson, Kerrie; Röttgers, Silja; Schrauder, André; Rosemann, Annegret; Irving, Julie; Stam, Ronald W.; Shultz, Leonard D.; Harbott, Jochen; Jürgens, Heribert; Schrappe, Martin; Pieters, Rob; Vormoor, Josef

2008-01-01

362

The significance of PTEN and AKT aberrations in pediatric T-cell acute lymphoblastic leukemia  

PubMed Central

Background PI3K/AKT pathway mutations are found in T-cell acute lymphoblastic leukemia, but their overall impact and associations with other genetic aberrations is unknown. PTEN mutations have been proposed as secondary mutations that follow NOTCH1-activating mutations and cause cellular resistance to ?-secretase inhibitors. Design and Methods The impact of PTEN, PI3K and AKT aberrations was studied in a genetically well-characterized pediatric T-cell leukemia patient cohort (n=146) treated on DCOG or COALL protocols. Results PTEN and AKT E17K aberrations were detected in 13% and 2% of patients, respectively. Defective PTEN-splicing was identified in incidental cases. Patients without PTEN protein but lacking exon-, splice-, promoter mutations or promoter hypermethylation were present. PTEN/AKT mutations were especially abundant in TAL- or LMO-rearranged leukemia but nearly absent in TLX3-rearranged patients (P=0.03), the opposite to that observed for NOTCH1-activating mutations. Most PTEN/AKT mutant patients either lacked NOTCH1-activating mutations (P=0.006) or had weak NOTCH1-activating mutations (P=0.011), and consequently expressed low intracellular NOTCH1, cMYC and MUSASHI levels. T-cell leukemia patients without PTEN/AKT and NOTCH1-activating mutations fared well, with a cumulative incidence of relapse of only 8% versus 35% for PTEN/AKT and/or NOTCH1-activated patients (P=0.005). Conclusions PI3K/AKT pathway aberrations are present in 18% of pediatric T-cell acute lymphoblastic leukemia patients. Absence of strong NOTCH1-activating mutations in these cases may explain cellular insensitivity to ?-secretase inhibitors. PMID:22491738

Zuurbier, Linda; Petricoin, Emanuel F.; Vuerhard, Maartje J.; Calvert, Valerie; Kooi, Clarissa; Buijs-Gladdines, Jessica G.C.A.M.; Smits, Willem K.; Sonneveld, Edwin; Veerman, Anjo J.P.; Kamps, Willem A.; Horstmann, Martin; Pieters, Rob; Meijerink, Jules P.P.

2012-01-01

363

Detection of mRNA for the tax1\\/rex1 Gene of Human T-Cell Leukemia Virus Type I in Fresh Peripheral Blood Mononuclear Cells of Adult T-Cell Leukemia Patients And Viral Carriers by Using the Polymerase Chain Reaction  

Microsoft Academic Search

Expression of human T-cell leukemia virus type I (HTLV-I) is not detectable by immunofluorescence analysis or RNA blot analysis in most fresh peripheral blood mononuclear cells of patients with adult T-cell leukemia or of asymptomatic HTLV-I carriers. However, in this work, mRNA for the HTLV-I tax1\\/rex1 genes was detected in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients

Tomohiro Kinoshita; Masanori Shimoyama; Kensei Tobinai; Mizuko Ito; Shin-Ichiro Ito; Shuichi Ikeda; Kazuo Tajima; Kunitada Shimotohno; Takashi Sugimura

1989-01-01

364

Transfection of antisense core 2 ?1,6-N-acetylglucosaminyltransferase-1 cDNA suppresses selectin ligand expression and tissue infiltration of B-cell precursor leukemia cells  

Microsoft Academic Search

B-cell precursor (BCP) leukemia cells infiltrate into peripheral organs and the disease often relapses. Inhibition of tissue infiltration may improve the treatment outcome of BCP-leukemia patients. Selectin ligand has been suggested to play an important role in the infiltration of leukemia cells. However, the regulation mechanisms and involvement in tissue infiltration of selectin ligand expression in BCP-leukemia cells are not

J Kikuchi; H Ozaki; C Nonomura; H Shinohara; S Iguchi; H Nojiri; H Hamada; A Kiuchi; M Nakamura

2005-01-01

365

Exploiting T cells specific for human minor histocompatibility antigens for therapy of leukemia  

Microsoft Academic Search

Minor histocompatibility (H) antigens are major targets of a graft-versus-leukemia (GVL) effect mediated by donor CD8+ and CD4+ T cells following allogeneic hematopoietic cell transplantation (HCT) between human leukocyte antigen identical individuals. In the 15 years since the first molecular characterization of human minor H antigens, significant strides in minor H antigen discovery have been made as a consequence of

Marie Bleakley; Stanley R Riddell

2011-01-01

366

Curcumin, an antioxidant and anti-tumor promoter, induces apoptosis in human leukemia cells  

Microsoft Academic Search

Curcumin, widely used as a spice and coloring agent in food, possesses potent antioxidant, anti-inflammatory and anti-tumor promoting activities. In the present study, curcumin was found to induce apoptotic cell death in promyelocytic leukemia HL-60 cells at concentrations as low as 3.5 ?g\\/ml. The apoptosis-inducing activity of curcumin appeared in a dose- and time-dependent manner. Flow cytometric analysis showed that

Min-Liang Kuo; Tze-Sing Huang

1996-01-01

367

In Childhood Acute Lymphoblastic Leukemia, Blasts at Different Stages of Immunophenotypic Maturation Have Stem Cell Properties  

Microsoft Academic Search

We examined the leukemic stem cell potential of blasts at different stages of maturation in childhood acute lymphoblastic leukemia (ALL). Human leukemic bone marrow was transplanted intrafemorally into NOD\\/scid mice. Cells sorted using the B precursor differentiation markers CD19, CD20, and CD34 were isolated from patient samples and engrafted mice before serial transplantation into primary or subsequent (up to quaternary)

Christoph le Viseur; Marc Hotfilder; Simon Bomken; Kerrie Wilson; Silja Röttgers; André Schrauder; Annegret Rosemann; Julie Irving; Ronald W. Stam; Leonard D. Shultz; Jochen Harbott; Heribert Jürgens; Martin Schrappe; Rob Pieters; Josef Vormoor

2008-01-01

368

Induction of Erythroid Differentiation and Modulation of Gene Expression by Tiazofurin in K-562 Leukemia Cells  

Microsoft Academic Search

Tiazofurin (2-beta -D-ribofuranosyl-4-thiazolecarboxamide; NSC 286193), an antitumor carbon-linked nucleoside that inhibits IMP dehydrogenase (IMP:NAD+ oxido-reductase; EC 1.1.1.205) and depletes guanylate levels, can activate the erythroid differentiation program of K-562 human leukemia cells. Tiazofurin-mediated cell differentiation is a multistep process. The inducer initiates early (<6 hr) metabolic changes that precede commitment to differentiation; among these early changes are decreases in IMP

Edith Olah; Yutaka Natsumeda; Tadashi Ikegami; Zsofia Kote; Margit Horanyi; Judit Szelenyi; Tibor Kremmer; Susan R. Hollan; Janos Sugar; George Weber

1988-01-01

369

Haploidentical hemopoietic stem cell transplantation for the treatment of high-risk leukemias: how NK cells make the difference.  

PubMed

T-cell-depleted hematopoietic stem cell (HSC) transplantation from an HLA-haploidentical relative (Haplo HSCT) may represent a suitable and effective transplant option, as it is capable of rescuing not only adult patients with high-risk acute myeloid leukemias (AML) but also children with relapsed acute lymphoblastic leukemia (ALL), as shown by the two representative cases presented in this study. In Haplo HSCT, the anti-leukemia effect is mediated by "alloreactive" (i.e. KIR/HLA-mismatched) NK cells originated from donor HSCs. The availability of suitable KIR-specific monoclonal antibodies allows the prompt identification of alloreactive NK cell subsets as well as their quantification. This is important for selection of the most suitable donor and evaluation of the generation and persistence of these alloreactive NK cells after transplantation. In view of the favorable clinical outcome of children with chemo-resistant ALL, Haplo HSCT from an NK-alloreactive relative could become a first option in these high-risk leukemia patients. PMID:19481979

Locatelli, Franco; Pende, Daniela; Maccario, Rita; Mingari, Maria Cristina; Moretta, Alessandro; Moretta, Lorenzo

2009-11-01

370

AMD3100 disrupts the cross-talk between chronic lymphocytic leukemia cells and a mesenchymal stromal or nurse-like cell-based microenvironment: pre-clinical evidence for its association with chronic lymphocytic leukemia treatments  

PubMed Central

Background Interactions with the microenvironment, such as bone marrow mesenchymal stromal cells and nurse-like cells, protect chronic lymphocytic leukemia cells from spontaneous and drug-induced apoptosis. This protection is partially mediated by the chemokine SDF-1? (CXCL12) and its receptor CXCR4 (CD184) present on the chronic lymphocytic leukemia cell surface. Design and Methods Here, we investigated the ability of AMD3100, a CXCR4 antagonist, to sensitize chronic lymphocytic leukemia cells to chemotherapy in a chronic lymphocytic leukemia/mesenchymal stromal cell based or nurse-like cell based microenvironment co-culture model. Results AMD3100 decreased CXCR4 expression signal (n=15, P=0.0078) and inhibited actin polymerization/migration in response to SDF-1? (n=8, P<0.01) and pseudoemperipolesis (n=10, P=0.0010), suggesting that AMD3100 interferes with chronic lymphocytic leukemia cell trafficking. AMD3100 did not have a direct effect on apoptosis when chronic lymphocytic leukemia cells were cultured alone (n=10, P=0.8812). However, when they were cultured with SDF-1?, mesenchymal stromal cells or nurse-like cells (protecting them from apoptosis, P<0.001), chronic lymphocytic leukemia cell pre-treatment with AMD3100 significantly inhibited these protective effects (n=8, P<0.01) and decreased the expression of the anti-apoptotic proteins MCL-1 and FLIP. Furthermore, combining AMD3100 with various drugs (fludarabine, cladribine, valproïc acid, bortezomib, flavopiridol, methylprednisolone) in our mesenchymal stromal cell co-culture model enhanced drug-induced apoptosis (n=8, P<0.05) indicating that AMD3100 could mobilize chronic lymphocytic leukemia cells away from their protective microenvironment, making them more accessible to conventional therapies. Conclusions Taken together, these data demonstrate that interfering with the SDF-1?/CXCR4 axis by using AMD3100 inhibited chronic lymphocytic leukemia cell trafficking and microenvironment-mediated protective effects. Combining AMD3100 with other drugs may, therefore, represent a promising therapeutic approach to kill chronic lymphocytic leukemia cells. PMID:22058221

Stamatopoulos, Basile; Meuleman, Nathalie; De Bruyn, Cécile; Pieters, Karlien; Mineur, Philippe; Le Roy, Christine; Saint-Georges, Stéphane; Varin-Blank, Nadine; Cymbalista, Florence; Bron, Dominique; Lagneaux, Laurence

2012-01-01

371

Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma  

ClinicalTrials.gov

Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Lymphoma; Childhood Nasal Type Extranodal NK/T-Cell Lymphoma; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

2014-12-04

372

Efficacy of ponatinib against ABL tyrosine kinase inhibitor-resistant leukemia cells  

SciTech Connect

Highlights: •Efficacy of ponatinib against ABL tyrosine kinase inhibitor-resistant leukemia cells okabe et al. •Imatinib or nilotinib resistance was involved Src family kinase. •The BCR-ABL point mutation (E334V) was highly resistant to imatinib or nilotinib. •Ponatinib was a powerful strategy against imatinib or nilotinib resistant Ph-positive cells. -- Abstract: Because a substantial number of patients with chronic myeloid leukemia acquire resistance to ABL tyrosine kinase inhibitors (TKIs), their management remains a challenge. Ponatinib, also known as AP24534, is an oral multi-targeted TKI. Ponatinib is currently being investigated in a pivotal phase 2 clinical trial. In the present study, we analyzed the molecular and functional consequences of ponatinib against imatinib- or nilotinib-resistant (R) K562 and Ba/F3 cells. The proliferation of imatinib- or nilotinib-resistant K562 cells did not decrease after treatment with imatinib or nilotinib. Src family kinase Lyn was activated. Point mutation Ba/F3 cells (E334 V) were also highly resistant to imatinib and nilotinib. Treatment with ponatinib for 72 h inhibited the growth of imatinib- and nilotinib-resistant cells. The phosphorylation of BCR-ABL, Lyn, and Crk-L was reduced. This study demonstrates that ponatinib has an anti-leukemia effect by reducing ABL and Lyn kinase activity and this information may be of therapeutic relevance.

Okabe, Seiichi, E-mail: okabe@tokyo-med.ac.jp; Tauchi, Tetsuzo; Tanaka, Yuko; Ohyashiki, Kazuma

2013-06-07

373

Apoptosis of K562 leukemia cells by Abnobaviscum F®, a European mistletoe extract.  

PubMed

Evidence suggests that mistletoe extract has the potential to be used as an anticancer agent. Abnobaviscum F® is a European mistletoe extract from the host tree Fraxinus. We investigated the effect of Abnobaviscum F on the growth and survival of different leukemia cell lines. Abnobaviscum F treatment strongly reduced survival and induced apoptosis of K562 (human myeloid leukemia), RPMI-8226 (human plasmacytoma) and L1210 (murine lymphocytic leukemia) cells in culture. Using K562 cells to further investigate the mechanism of action of Abnobaviscum F, we showed that Abnobaviscum F-induced cell death was associated with the activation of caspase-9, JNK-1/2 and p38 MAPK, as well as with the downregulation of Mcl-1, and inhibition of ERK-1/2 and PKB phosphorylation. Moreover, Abnobaviscum F treatment led to both a reduction of cellular glutathione (GSH) and the induction of ER stress (GRP78 and CHOP induction and eIF-2? phosphorylation). By contrast, Abnobaviscum F did not impact the expression of the DR4 and DR5 death receptors. The Abnobaviscum F-induced apoptosis of K562 cells was blocked by pretreatment with either GSH, z-VAD-fmk or SP600125. Our results, therefore, show that Abnobaviscum F induces apoptosis of K562 cells through the activation of the intrinsic caspase pathway, the phosphorylation of JNK-1, the reduction of cellular GSH, and the induction of ER stress. PMID:22972372

Park, Yu-Kyoung; Do, Young Rok; Jang, Byeong-Churl

2012-12-01

374

Hepatic leukemia factor promotes resistance to cell death: Implications for therapeutics and chronotherapy  

SciTech Connect

Physiological variation related to circadian rhythms and aberrant gene expression patterns are believed to modulate therapeutic efficacy, but the precise molecular determinants remain unclear. Here we examine the regulation of cell death by hepatic leukemia factor (HLF), which is an output regulator of circadian rhythms and is aberrantly expressed in human cancers, using an ectopic expression strategy in JB6 mouse epidermal cells and human keratinocytes. Ectopic HLF expression inhibited cell death in both JB6 cells and human keratinocytes, as induced by serum-starvation, tumor necrosis factor alpha and ionizing radiation. Microarray analysis indicates that HLF regulates a complex multi-gene transcriptional program encompassing upregulation of anti-apoptotic genes, downregulation of pro-apoptotic genes, and many additional changes that are consistent with an anti-death program. Collectively, our results demonstrate that ectopic expression of HLF, an established transcription factor that cycles with circadian rhythms, can recapitulate many features associated with circadian-dependent physiological variation. - Highlights: ? Circadian-dependent physiological variation impacts therapeutic efficacy. ? Hepatic leukemia factor inhibits cell death and is a candidate circadian factor. ? Hepatic leukemia factor anti-death program is conserved in murine and human cells. ? Transcriptomics indicates the anti-death program results from a systems response.

Waters, Katrina M. [Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, Richland, WA 99354 (United States); Sontag, Ryan L. [Systems Toxicology Groups, Pacific Northwest National Laboratory, Richland, WA 99354 (United States); Weber, Thomas J., E-mail: Thomas.Weber@pnl.gov [Systems Toxicology Groups, Pacific Northwest National Laboratory, Richland, WA 99354 (United States)

2013-04-15

375

Disruption of SIRP? signaling in macrophages eliminates human acute myeloid leukemia stem cells in xenografts  

PubMed Central

Although tumor surveillance by T and B lymphocytes is well studied, the role of innate immune cells, in particular macrophages, is less clear. Moreover, the existence of subclonal genetic and functional diversity in some human cancers such as leukemia underscores the importance of defining tumor surveillance mechanisms that effectively target the disease-sustaining cancer stem cells in addition to bulk cells. In this study, we report that leukemia stem cell function in xenotransplant models of acute myeloid leukemia (AML) depends on SIRP?-mediated inhibition of macrophages through engagement with its ligand CD47. We generated mice expressing SIRP? variants with differential ability to bind human CD47 and demonstrated that macrophage-mediated phagocytosis and clearance of AML stem cells depend on absent SIRP? signaling. We obtained independent confirmation of the genetic restriction observed in our mouse models by using SIRP?-Fc fusion protein to disrupt SIRP?–CD47 engagement. Treatment with SIRP?-Fc enhanced phagocytosis of AML cells by both mouse and human macrophages and impaired leukemic engraftment in mice. Importantly, SIRP?-Fc treatment did not significantly enhance phagocytosis of normal hematopoietic targets. These findings support the development of therapeutics that antagonize SIRP? signaling to enhance macrophage-mediated elimination of AML. PMID:22945919

Theocharides, Alexandre P.A.; Jin, Liqing; Cheng, Po-Yan; Prasolava, Tatiana K.; Malko, Andrei V.; Ho, Jenny M.; Poeppl, Armando G.; van Rooijen, Nico; Minden, Mark D.; Danska, Jayne S.; Dick, John E.

2012-01-01

376

Adipocytes cause leukemia cell resistance to L-asparaginase via release of glutamine.  

PubMed

Obesity is a significant risk factor for cancer. A link between obesity and a childhood cancer has been identified: obese children diagnosed with high-risk acute lymphoblastic leukemia (ALL) had a 50% greater risk of relapse than their lean counterparts. l-asparaginase (ASNase) is a first-line therapy for ALL that breaks down asparagine and glutamine, exploiting the fact that ALL cells are more dependent on these amino acids than other cells. In the present study, we investigated whether adipocytes, which produce significant quantities of glutamine, may counteract the effects of ASNase. In children being treated for high-risk ALL, obesity was not associated with altered plasma levels of asparagine or glutamine. However, glutamine synthetase was markedly increased in bone marrow adipocytes after induction chemotherapy. Obesity substantially impaired ASNase efficacy in mice transplanted with syngeneic ALL cells and, like in humans, without affecting plasma asparagine or glutamine levels. In coculture, adipocytes inhibited leukemic cell cytotoxicity induced by ASNase, and this protection was dependent on glutamine secretion. These findings suggest that adipocytes work in conjunction with other cells of the leukemia microenvironment to protect leukemia cells during ASNase treatment. PMID:23585457

Ehsanipour, Ehsan A; Sheng, Xia; Behan, James W; Wang, Xingchao; Butturini, Anna; Avramis, Vassilios I; Mittelman, Steven D

2013-05-15

377

Adipocytes Cause Leukemia Cell Resistance to L-Asparaginase via Release of Glutamine  

PubMed Central

Obesity is a significant risk factor for cancer. A link between obesity and a childhood cancer has been identified: obese children diagnosed with high-risk acute lymphoblastic leukemia (ALL) had a 50% greater risk of relapse than their lean counterparts. L-asparaginase (ASNase) is a first-line therapy for ALL that breaks down asparagine and glutamine, exploiting the fact that ALL cells are more dependent on these amino acids than other cells. In the present study, we investigated whether adipocytes, which produce significant quantities of glutamine, may counteract the effects of ASNase. In children being treated for high-risk ALL, obesity was not associated with altered plasma levels of asparagine or glutamine. However, glutamine synthetase was markedly increased in bone marrow adipocytes after induction chemotherapy. Obesity substantially impaired ASNase efficacy in mice transplanted with syngeneic ALL cells, and, like in humans, without affecting plasma asparagine or glutamine levels. In co-culture, adipocytes inhibited leukemic cell cytotoxicity induced by ASNase, and this protection was dependent on glutamine secretion. These findings suggest that adipocytes work in conjunction with other cells of the leukemia microenvironment to protect leukemia cells during ASNase treatment. PMID:23585457

Ehsanipour, Ehsan A.; Sheng, Xia; Behan, James W.; Wang, Xingchao; Butturini, Anna; Avramis, Vassilios I.; Mittelman, Steven D.

2013-01-01

378

Rituximab, Rasburicase, and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Advanced B-Cell Leukemia or Lymphoma  

ClinicalTrials.gov

Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Small Noncleaved Cell Lymphoma; Stage II Childhood Large Cell Lymphoma; Stage II Childhood Small Noncleaved Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Childhood Small Noncleaved Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma; Stage IV Childhood Small Noncleaved Cell Lymphoma; Untreated Childhood Acute Lymphoblastic Leukemia

2014-09-10

379

PCFT/SLC46A1 promoter methylation and restoration of gene expression in human leukemia cells  

SciTech Connect

The proton-coupled folate transporter (PCFT/SLC46A1) displays optimal and prominent folate and antifolate transport activity at acidic pH in human carcinoma cells but poor activity in leukemia cells. Consistently herein, human leukemia cell lines expressed poor PCFT transcript levels, whereas various carcinoma cell lines showed substantial PCFT gene expression. We identified a CpG island with high density at nucleotides -200 through +100 and explored its role in PCFT promoter silencing. Leukemia cells with barely detectable PCFT transcripts consistently harbored 85-100% methylation of this CpG island, whereas no methylation was found in carcinoma cells. Treatment with 5-Aza-2'-deoxycytidine which induced demethylation but not with the histone deacetylase inhibitor trichostatin A, restored 50-fold PCFT expression only in leukemia cells. These findings constitute the first demonstration of the dominant epigenetic silencing of the PCFT gene in leukemia cells. The potential translational implications of the restoration of PCFT expression in chemotherapy of leukemia are discussed.

Gonen, Nitzan; Bram, Eran E. [Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Assaraf, Yehuda G. [Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion-Israel Institute of Technology, Haifa 32000 (Israel)], E-mail: assaraf@tx.technion.ac.il

2008-11-28

380

Myeloid cell leukemia-1 regulates the cell growth and predicts prognosis in gastric cancer.  

PubMed

The expression of myeloid cell leukemia-1 (Mcl?1), a member of the anti-apoptotic Bcl-2 protein family, has been associated with tumor progression and adverse patient outcome. The aims of current study were to evaluate whether Mcl-1 affects the survival or death of gastric cancer cells, and to investigate the prognostic value of its expression in gastric cancer. PcDNA3.1-Mcl-1 expression and Mcl-1 siRNA vectors were used to overexpress and silence Mcl-1 expression in gastric cancer cell lines including SNU638 and TMK1, respectively. Immunohistochemistry was used to determine the expression of Mcl-1 in gastric cancer tissues. Apoptosis was determined by the TUNEL assay, and cell proliferation was determined by immunostaining with a Ki-67 antibody. Mcl-1 knockdown induced apoptosis through the upregulation of caspase-3, and -7, and PARP activity, and the release of Smac/DIABLO and Omi/HtrA2 into the cytoplasm. Additionally, cell cycle arrest occurred due to decrease of cyclin D1, cell division cycle gene 2 (cdc2), and cyclin-dependent kinase 4 and 6. In contrast, overexpression of Mcl-1 inhibited apoptosis and cell cycle arrest. Mcl-1 knockdown did not suppress tumor cell proliferation in gastric cancer cells, whereas overexpression of Mcl-1 enhanced tumor cell proliferation. The JAK2 and STAT3 signaling cascades were significantly blocked by Mcl-1 knockdown. The mean Ki-67 labeling index (KI) value of Mcl-1 positive tumors was significantly lower than that of Mcl-1 negative tumors. However, there was no significant difference between Mcl-1 expression and the apoptotic index (AI). Mcl-1 expression was significantly increased in gastric cancer tissues compared to normal gastric mucosa tissues, and was associated with age, tumor size, stage, depth of invasion, lymph node metastasis and poor survival. Our study showed that Mcl-1 regulates the cell growth and might be a potential prognostic marker for gastric cancer. PMID:25672320

Lee, Wan-Sik; Park, Young-Lan; Kim, Nuri; Oh, Hyung-Hoon; Son, Dong-Jun; Kim, Mi-Young; Oak, Chan-Young; Chung, Cho-Yun; Park, Hyung-Chul; Kim, Jong-Sun; Myung, Dae-Seong; Cho, Sung-Bum; Joo, Young-Eun

2015-05-01

381

Trophoblast Cell Line Conditioned Medium for in Vitro Culture and Antigenic Characterization of Acute Myeloid Leukemia Clonogenic Cells1  

Microsoft Academic Search

The colony-stimulating factor-containing supernatant of the human trophoblast cell line TPA-30-1 was used to stimulate in vitro growth of acute myeloid leukemia clonogenic cells from 54 patients. Prevalent colonygrowth ( 10-> 10(10)was observed in 63% of cases. In 31% clusters and a few colonies (1-9\\/1 x 10*plated cells) were scored. Neither colonies nor clusters could be detected in the remaining

Patrizia Pregno; Corrado Tarella; Francis W. Ruscetti; Alessandro Pileri; Eugenio Gallo

1987-01-01

382

Human Promyelocytic Leukemia Cells in Culture Differentiate into Macrophage-Like Cells when Treated with a Phorbol Diester  

Microsoft Academic Search

When suspension cultures of human promyelocytic leukemia cells (line HL60) were treated with 12-O-tetradecanoylphorbol 13-acetate (TPA; 1.6-160 nM), more than 80% of the cells adhered to the plastic substrate within 24 hr. Within the same time period the immature azurophilic granulations typical of HL60 promyelocytic cells disappeared and the nuclear chromatin became more condensed, but the nucleolus was retained. The

Giovanni Rovera; Daniela Santoli; Caroline Damsky

1979-01-01

383

Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia  

ClinicalTrials.gov

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

2015-01-29

384

Ganoderma lucidum Polysaccharides Induce Macrophage-like Differentiation in Human Leukemia THP1 Cells via Caspase and p53 Activation  

Microsoft Academic Search

Differentiation therapy by induction of tumor cells is an important method in the treatment of hematological cancers such as leukemia. Tumor cell differentiation ends cancer cells' immor- tality, thus stopping cell growth and proliferation. In our previous study, we found that fucose- containing polysaccharide fraction F3 extracted from Ganoderma lucidum can bring about cytokine secretion and cell death in human

Jia-Wei Hsu; Hsuan-Cheng Huang; Shui-Tein Chen; Chi-Huey Wong; Hsueh-Fen Juan

2009-01-01

385

Metabolic Adaptation to Chronic Inhibition of Mitochondrial Protein Synthesis in Acute Myeloid Leukemia Cells  

PubMed Central

Recently, we demonstrated that the anti-bacterial agent tigecycline preferentially induces death in leukemia cells through the inhibition of mitochondrial protein synthesis. Here, we sought to understand mechanisms of resistance to tigecycline by establishing a leukemia cell line resistant to the drug. TEX leukemia cells were treated with increasing concentrations of tigecycline over 4 months and a population of cells resistant to tigecycline (RTEX+TIG) was selected. Compared to wild type cells, RTEX+TIG cells had undetectable levels of mitochondrially translated proteins Cox-1 and Cox-2, reduced oxygen consumption and increased rates of glycolysis. Moreover, RTEX+TIG cells were more sensitive to inhibitors of glycolysis and more resistant to hypoxia. By electron microscopy, RTEX+TIG cells had abnormally swollen mitochondria with irregular cristae structures. RNA sequencing demonstrated a significant over-representation of genes with binding sites for the HIF1?:HIF1? transcription factor complex in their promoters. Upregulation of HIF1? mRNA and protein in RTEX+TIG cells was confirmed by Q-RTPCR and immunoblotting. Strikingly, upon removal of tigecycline from RTEX+TIG cells, the cells re-established aerobic metabolism. Levels of Cox-1 and Cox-2, oxygen consumption, glycolysis, mitochondrial mass and mitochondrial membrane potential returned to wild type levels, but HIF1? remained elevated. However, upon re-treatment with tigecycline for 72 hours, the glycolytic phenotype was re-established. Thus, we have generated cells with a reversible metabolic phenotype by chronic treatment with an inhibitor of mitochondrial protein synthesis. These cells will provide insight into cellular adaptations used to cope with metabolic stress. PMID:23520503

Jhas, Bozhena; Sriskanthadevan, Shrivani; Skrtic, Marko; Sukhai, Mahadeo A.; Voisin, Veronique; Jitkova, Yulia; Gronda, Marcela; Hurren, Rose; Laister, Rob C.; Bader, Gary D.; Minden, Mark D.; Schimmer, Aaron D.

2013-01-01

386

Incidence of adult T-cell leukemia/lymphoma in nonendemic areas.  

PubMed

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm with extremely poor prognosis caused by human T-cell leukemia virus type 1 (HTLV-1). The distribution of HTLV-1 and the incidence of ATLL in endemic areas have been well described, however, little is known about the incidences and the trends of the disease in nonendemic areas. Recently, studies have shown that the HTLV-1 carriers are increasing in nonendemic areas. Also, the incidence of ATLL seems to be significantly increasing in nonendemic areas suggesting that HTLV-1 carriers have emigrated from endemic areas. These epidemiologic studies indicate the necessity of edification of the disease caused by HTLV-1 and establishing appropriate preventive methods against infection in nonendemic areas. PMID:25762122

Yoshida, Noriaki; Chihara, Dai

2015-02-01

387

Critical molecular pathways in cancer stem cells of chronic myeloid leukemia  

PubMed Central

Inhibition of BCR-ABL with kinase inhibitors in the treatment of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) is highly effective in controlling but not curing the disease. This is largely due to the inability of these kinase inhibitors to kill leukemia stem cells (LSCs) responsible for disease relapse. This stem cell resistance is not associated with the BCR-ABL kinase domain mutations resistant to kinase inhibitors. Development of curative therapies for CML requires the identification of critical molecular pathways responsible for the survival and self-renewal of LSCs. In this review, we will discuss our current understanding of these critical molecular pathways in LSCs and the available therapeutic strategies for targeting these stem cells in CML. PMID:20574455

Chen, Yaoyu; Peng, Cong; Sullivan, Con; Li, Dongguang; Li, Shaoguang

2011-01-01

388

Temple scientists find drug resistant stem cells may be source of genetic chaos, DNA damage in leukemia  

Cancer.gov

An international team of scientists, led by researchers from Temple University School of Medicine (home to the Fox Chase Cancer Center), has found that a source of mounting genomic chaos, or instability, common to chronic myeloid leukemia (CML) may lie in a pool of leukemia stem cells that are immune to treatment with potent targeted anticancer drugs. They have shown in mice with cancer that even after treatment with the highly effective imatinib (Gleevec), stem cells that become resistant to these drugs – tyrosine kinase inhibitors (TKIs) – may continue to foster DNA damage, potentially leading to disease relapse and a downward spiral to a much more deadly “blast” stage of leukemia.

389

Core Transcriptional Regulatory Circuit Controlled by the TAL1 Complex in Human T Cell Acute Lymphoblastic Leukemia  

E-print Network

The oncogenic transcription factor TAL1/SCL is aberrantly expressed in over 40% of cases of human T cell acute lymphoblastic leukemia (T-ALL), emphasizing its importance in the molecular pathogenesis of T-ALL. Here we ...

Sanda, Takaomi

390

Washington U researchers find that many older people have mutations linked to leukemia, lymphoma in their blood cells  

Cancer.gov

At least 2 percent of people over age 40 and 5 percent of people over 70 have mutations linked to leukemia and lymphoma in their blood cells, according to new research at Washington University School of Medicine in St. Louis.

391

In vitro study on influence of a discrete nano-hydroxyapatite on leukemia P388 cell behavior.  

PubMed

Influence of a discrete nano-hydroxyapatite crystal (nano-HAp) on lymphatic leukemia P388 cell behavior was investigated by an in vitro technique using an MTT test and FITC analysis. The discrete nano-HAp was prepared by decanting upside clear layer of the nano-HAp suspension which was synthesized by a wet method using calcium hydroxide suspension and phosphoric acid solutions. The nano-HAp was identified as hydroxyapatite by the X-ray powder diffraction pattern and an infrared spectroscopy. The nano-HAp with concentrations of 8-40 microg/ml was dispersed into PRMI 1640 media with leukemia cells derived from BALB/C mice. The survival ratio of the cells decreased with the amounts of the nano-HAp increasing. Apoptosis rates of leukemia P388 cells on co-culturing with the nano-HAp of 35 microg/ml for 24, 48 h were 14.5% and 45.8%, respectively, and higher than those of 10.4% and 34% in controls. The G0/G1 peak values in leukemia P388 cell cycle were declined to reduce and the S peak values increased with extension time of co-culture. These results proved that the discrete nano-HAp can cause apoptosis of the leukemia P388 cells, and selectively act on G1 phase and arrest the G1 phase in cell cycle of the leukemia P388. PMID:17851174

Li, G; Huang, J; Li, Y; Zhang, R; Deng, B; Zhang, J; Aoki, H

2007-01-01

392

Transferrin as a drug carrier: Cytotoxicity, cellular uptake and transport kinetics of doxorubicin transferrin conjugate in the human leukemia cells.  

PubMed

Leukemias are one of most common malignancies worldwide. There is a substantial need for new chemotherapeutic drugs effective against this cancer. Doxorubicin (DOX), used for treatment of leukemias and solid tumors, is poorly efficacious when it is administered systemically at conventional doses. Therefore, several strategies have been developed to reduce the side effects of this anthracycline treatment. In this study we compared the effect of DOX and doxorubicin-transferrin conjugate (DOX-TRF) on human leukemia cell lines: chronic erythromyeloblastoid leukemia (K562), sensitive and resistant (K562/DOX) to doxorubicin, and acute lymphoblastic leukemia (CCRF-CEM). Experiments were also carried out on normal cells, peripheral blood mononuclear cells (PBMC). We analyzed the chemical structure of DOX-TRF conjugate by using mass spectroscopy. The in vitro growth-inhibition assay XTT, indicated that DOX-TRF is more cytotoxic for leukemia cells sensitive and resistant to doxorubicin and significantly less sensitive to normal cells compared to DOX alone. During the assessment of intracellular DOX-TRF accumulation it was confirmed that the tested malignant cells were able to retain the examined conjugate for longer periods of time than normal lymphocytes. Comparison of kinetic parameters showed that the rate of DOX-TRF efflux was also slower in the tested cells than free DOX. The results presented here should contribute to the understanding of the differences in antitumor activities of the DOX-TRF conjugate and free drug. PMID:24055890

Szwed, Marzena; Matusiak, Agnieszka; Laroche-Clary, Audrey; Robert, Jacques; Marszalek, Ilona; Jozwiak, Zofia

2014-03-01

393

Human NK cells: from surface receptors to the therapy of leukemias and solid tumors.  

PubMed

Natural Killer (NK) cells are major effector cells of the innate immunity. The discovery, over two decades ago, of major histocompatibility complex-class I-specific inhibitory NK receptors and subsequently of activating receptors, recognizing ligands expressed by tumor or virus-infected cells, paved the way to our understanding of the mechanisms of selective recognition and killing of tumor cells. Although NK cells can efficiently kill tumor cells of different histotypes in vitro, their activity may be limited in vivo by their inefficient trafficking to tumor lesions and by the inhibition of their function induced by tumor cells themselves and by the tumor microenvironment. On the other hand, the important r