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1

Hairy cell leukemia  

Microsoft Academic Search

In 24 patients with hairy cell leukemia, histological and fine structural findings from biopsies of the bone marrow are reported and their validity is compared with other diagnostic procedures available. Diagnosis by light microscopy of anterior iliac crest biopsies obtained by the method of myelotomy is possible with a high degree of accuracy. The differentiation of hairy cell leukemia from

K. F. Vykoupil; J. Thiele; A. Georgii

1976-01-01

2

Hairy Cell Leukemia Variant  

Microsoft Academic Search

A 59-year-old man presented with lymphocytosis with huge splenomegaly. The abnormal lymphocytes had a high nucleoplasmxytoplasm ratio, a prominent nucleolus and hairy cytoplasmic projections. Immunophenotyping revealed B-cell leukemia with negative reactions to CD5 and CD25. Cytogenetic study showed 46, XY, der(5)t(5;6)(q35;p21), del(7)(p13)\\/ 46, idem, add(22)(q13). The patient did not respond to chlorambucil and a combination of cyclophosphamide, vincristine and prednisolone.

Po Dunn; Lee-Yung Shih; Yat-Sen Ho; Hwai-Fang Tien

1995-01-01

3

Vasculitides in hairy cell leukemia  

Microsoft Academic Search

Forty-two cases of vasculitis coincident with hairy cell leukemia (HCL) havebeen reported, of which 17 had panarteritis nodosa (PAN), 21 had cutaneous leukocytoclastic vasculitis (LCV), and 4 had vessel wall infiltration by hairy cells. PAN generally occurred after the diagnosis of HCL, splenectomy, and infection. HBs antigen was detected in 3 of 12 patients tested, whereas immune complexes were positive

Paul Hasler; Hansjörg Kistler; Heini Gerber

1995-01-01

4

General Information about Hairy Cell Leukemia  

MedlinePLUS

General Information About Hairy Cell Leukemia Hairy cell leukemia is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white ... platelets. Yellow marrow is made mostly of fat. Leukemia may affect red blood cells, white blood cells, ...

5

Hairy cell leukemia  

MedlinePLUS

... of normal blood cells. The cause of this disease is unknown, although certain genetic changes (mutations) in the cancer cells have been found. It affects men more often than women. The average age of diagnosis is 55.

6

Hairy cell leukemia in father and son.  

PubMed

Hairy cell leukemia (HCL) is an uncommon B cell disorder, and familial HCL is rarely encountered among the first degree relatives of HCL patients. A father and son, both of whom developed hairy cell leukemia, is presented in this report. The HLA haplotype shared by the father and son was A2, B18, BW6, CW7, DR3, DR10, and DQ8. Among these haplotypes, HLA A2 and Bw6 have previously been reported. PMID:14716034

Cetiner, Mustafa; Adigüzel, Cafer; Argon, Dilek; Ratip, Siret; Eksioglu-Demiralp, Emel; Tecimer, Tulay; Bayik, Mahmut

2003-01-01

7

Scanning Immunoelectron Microscopy of Hairy Cell Leukemia  

Microsoft Academic Search

Scanning electron microscopy has shown a typical cell surface morphology in hairy cell leukemia. Scanning immunoelectron microscope techniques, utilizing monoclonal antibodies and colloidal gold particles, have recently become available. Eight patients with hairy cell leukemia have been studied with a panel of monoclonal antibodies of which Bl, BA1, OKM1, anti-TAC and LeuM5 were shown to be suitable for scanning immunoelectron

D. Soligo; G. Lambertenghi-Deliliers; M. T. Nava; N. Polli; G. Cattoretti; E. E. Polli

1985-01-01

8

Hairy cell leukemia (Leukemic reticuloendotheliosis). II. Ultrastructure of the spleen  

Microsoft Academic Search

Seven surgically removed spleens from patients with hairy cell leukemia and hypersplenism were examined ultrastructurally. In all spleens the pulp cords were diffusely and compactly infiltrated by hairy cells. Numerous hairy cells were also evident in the often distended sinuses. The hairy projections were readily visible in electron micrographs and tended to interdigitate to form syncytium-like aggregates. Compression of hairy

Jerome S. Burke; Bruce Mackay; Henry Rappaport

1976-01-01

9

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.

10

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

11

Hairy Cell Leukemia (‘Leukemic Reticuloendotheliosis’), Reticulosarcoma, and Monocytic Leukemia  

Microsoft Academic Search

Cytochemical and electron-microscopic studies have been carried out on leukemic monocytes and ‘hairy cells’ (HC), ‘reticulosarcoma’ (RS) cells and cells of cases of ‘reticulosis’ and ‘reticulosarcoma cell leukemia’. Additional investigations included quantitative determinations of the urinary lysozyme excretion, skin window studies, testing of the phagocytosis of ferritin by HC, and labelling of the Fc receptors on HC at the ultrastructural

F. Schmalzl; D. Huhn; H. Asamer; H. Braunsteiner

1975-01-01

12

Hairy cell leukemia: clinicopathological and immunophenotypic study.  

PubMed

Hairy cell leukemia (HCL) is a rare neoplasm of mature small B lymphoid cells with characteristic circumferential 'hairy projections' involving the peripheral blood, bone marrow and splenic red pulp. With the advent of immunophenotyping and newer treatment modalities, prolonged remission can be achieved after a definitive diagnosis. Due to the rarity of this condition and presence of only a few case series from India, this work was undertaken. The aim was to study the clinico-pathologic and immunophenotypic features of all cases diagnosed as hairy cell leukemia. The cases were retrieved from Hematopathology records, between 1991 and 2012. The complete clinical details, investigations, treatment and follow-up were obtained from Medical Oncology records. The peripheral blood picture, bone marrow cytology and trephine sections along with special stains were reviewed. There were 12 cases of HCL during the study period with a M:F ratio of 11:1. Of these, ten were diagnosed as classical HCL and two as variant HCL. The most common clinical manifestations were fever, easy fatigability and weakness. Splenomegaly was present in 81.8 % cases. Though all the patients showed some form of cytopenia, there were three (25 %) patients with leucocytosis. The smears from all patients showed atypical lymphoid cells with circumferential hairy projections. TRAP was positive in 9 patients (81.8 %). Immunophenotyping was done in six cases, four were confirmed as HCL and two were diagnosed as HCL-v. The patients treated with Cladribine generally had a good response. The characteristic morphology of the hairy cells; along with correlation with the clinical features, TRAP positivity and immunophenotyping by flow cytometry is essential for diagnosis. Treatment response with Cladribine is good and has prolonged remission rates. PMID:25114404

Konkay, Kaumudi; Uppin, Megha S; Uppin, Shantveer G; Raghunadha Rao, D; Geetha, Ch; Paul, T Roshni

2014-09-01

13

Current therapeutic options in hairy cell leukemia.  

PubMed

Hairy cell leukemia (HCL) is a B-cell chronic lymphoproliferative disorder that was initially described as leukemic reticuloendotheliosis. The disease is characterized by monocytopenia, organomegaly, constitutional symptoms, and bone marrow fibrosis. Significant advances have improved the diagnosis and management of HCL over the last 55 years. Although HCL has an indolent course, most patients will require treatment of the disease. Indications to initiate therapy include disease-related symptoms, signs of bone marrow failure, or frequent infections. Asymptomatic patients without cytopenias can be observed without the need for therapeutic interventions. Therapeutic options usually consist of chemotherapy, immunotherapy, biological agents, and surgery. PMID:24971416

Mikler, Evgeny; Mascarenhas, John

2014-03-01

14

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

Federal Register 2010, 2011, 2012, 2013

...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

15

Leukemia - B-Cell Prolymphocytic Leukemia and Hairy Cell Leukemia  

MedlinePLUS

... Net Patient Education Video : View a short video led by an ASCO expert in leukemia that provides basic information and areas of research. To continue reading this guide, use the menu on the side of your screen to select another section. ‹ Leukemia - B-cell Prolymphocytic ...

16

Interferon in the treatment of hairy-cell leukemia  

Microsoft Academic Search

The introduction of alpha interferon in 1984 initiated a new and exciting turnaround in the treatment of hairy-cell leukemia. Until that time splenectomy was the only known effective therapy for this disease. Interferon proved to benefit hairy-cell leukemia patients with active disease, whether or not they had undergone prior splenectomy. However, most interferon-induced responses were partial and were of relatively

Kanti R Rai

2003-01-01

17

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.

18

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.

19

Rituximab in relapsed or refractory hairy cell leukemia  

Microsoft Academic Search

The purpose of this study was to investi- gate the efficacy and safety of the mono- clonal antibody, rituximab, in relapsed or refractory hairy cell leukemia (HCL). Fif- teen patients with relapsed or primary refractory HCL after nucleoside analogs received rituximab 375 mg\\/m2 weekly for a total of 8 planned doses. An additional 4 doses could be administered to respond-

Deborah A. Thomas; Susan O'Brien; Carlos Bueso-Ramos; Stefan Faderl; Michael J. Keating; Francis J. Giles; Jorge Cortes; Hagop M. Kantarjian

2003-01-01

20

Epidemiology of Hairy Cell Leukemia in Los Angeles County1  

Microsoft Academic Search

The descriptive epidemiológica! characteristics of hairy cell leukemia (HCL), a rare chronic lymphoproliferative disorder, were examined by using incidence data collected from 1972 to 1987 by the Cancer Surveil lance Program, the population-based cancer registry for Los Angeles County. During the study period, 208 incident cases of historically confirmed HCL were diagnosed. HCL comprised 2% of all leukemias diagnosed in

Leslie Bernstein; Patricia Newton; Ronald K. Ross

21

Hairy cell leukemia variant with t(2;8)(p12;q24) abnormality  

Microsoft Academic Search

Hairy cell leukemia variant is an uncommon chronic B-cell lymphoproliferative disorder characterized clinically by splenomegaly and marked leukocytosis. Cytologically, the leukemic cells are distinguishable from those of classical hairy cell leukemia by the presence of single, central, and vesicular nucleoli. Cytogenetic information for this uncommon leukemia is scanty, although structural abnormalities involving 7q34 have been reported in few cases. We

K. F. Wong; Y. L. Kwong; P. K. Hui

1997-01-01

22

Recombinant a-2Interferon for Hairy Cell Leukemia  

Microsoft Academic Search

Twenty-two patients with hairy cell leukemia were treated with biosynthetic (recombinant) a-2-interferon in an open- label. single-arm efficacy study. Patients received 2 x 106 U\\/rn2 recombinant a-2-interferon three times weekly. Therapy was well tolerated subjectively with minimal short-term hematologic toxicity. Two patients had bacte- rial infections during the period of study. and one patient experienced a short-lived readily reversible rejection

Andrew D. Jacobs; Richard E. Champlin; David W. Golde

2010-01-01

23

Radiation exposure as a possible etiologic factor in hairy cell leukemia (leukemic reticuloendotheliosis)  

SciTech Connect

The frequency of prior occupational, accidental, or therapeutic radiation exposure was significantly higher for hairy cell leukemia patients than for a control group of solid tumor patients. Hairy cell leukemia patients were also more frequently involved in occupations at high risk of radiation exposure such as chemist, engineer, physicist, and health care facility worker. The observation that the incidence of thyroid disorders among hairy cell leukemia patients was also unusually high was interpreted as further indirect evidence of excessive radiation exposure. It appears that radiation exposure may be an important contributing factor in the development of some cases of hairy cell leukemia.

Stewart, D.J.; Keating, M.J.

1980-10-01

24

Synthesis of a Peroxidase Activity by Cells of Hairy Cell Leukemia: A Study by Ultrastructural Cytochemistry  

Microsoft Academic Search

The nature of cells present in the blood, marrow, and spleen of patients with hairy cell leukemia is largely debated. These cells have been tentatively categorized on the basis of either monocytic or lymphocytic markers, and the accumulating data points to the fact that they share some characteris- tics of both cell types. Although hairy cells are known to lack

F. Reyes; M. F. Gourdin; J. P. Farcet; B. Dreyfus; J. Breton-Gorius

1978-01-01

25

Radiation exposure as a possible etiologic factor in hairy cell leukemia (leukemic reticuloendotheliosis)  

Microsoft Academic Search

The frequency of prior occupational, accidental, or therapeutic radiation exposure was significantly higher for hairy cell leukemia patients than for a control group of solid tumor patients. Hairy cell leukemia patients were also more frequently involved in occupations at high risk of radiation exposure such as chemist, engineer, physicist, and health care facility worker. The observation that the incidence of

David J. Stewart; Michael J. Keating

1980-01-01

26

A case report of hairy cell leukemia presenting concomitantly with sweet syndrome.  

PubMed

Hairy cell leukemia and Sweet syndrome are both uncommon hematological diagnoses. We present a patient who was admitted with fevers, pancytopenia, pneumonia, and rash. Diagnostic bone marrow biopsy demonstrates Hairy cell Leukemia and skin biopsy demonstrates neutrophils infiltration consistent with Sweet syndrome. The patient was treated with purine analogs with resolution of the cytopenias, infection, and rash. PMID:24715920

Alkayem, Mohammad; Cheng, Waina

2014-01-01

27

Hairy cell leukemia: Update on molecular profiling and therapeutic advances.  

PubMed

Hairy cell leukemia was initially described as a clinicopathologic entity more than 50 years ago. We have subsequently discovered that HCL is really at least two diseases: classical HCL and the hairy cell leukemia variant. The former is among a small group of cancers exceptional for being (nearly) unified by a single genetic lesion, the BRAF V600E mutation. Over the past three decades, tremendous progress in both diagnostic and prognostic clarification has been accompanied by therapeutic advances in classical HCL. Consequently, this once uniformly fatal disease has been converted in most cases into a chronic illness enabling patients to live long and productive lives. In response to standard therapy, patients have high complete remission rates. Unfortunately, the long-term survival curves have not plateaued, revealing that this disease is controlled but not cured. Though rare and representing only about 10% of an already rare disease, those patients with the variant fare exceptionally poorly with standard therapy: complete response rates to purine nucleoside analogs are reported to be less than 50%, whereas the complete response rates in classical HCL are up to 90%. Novel small molecules targeting BRAF and the B-cell receptor signaling complex, and biologic agents like antibodies and immunotoxin conjugates are being explored for those patients who have relapsed. Substantial opportunities for continued research remain. This complex and multi-faceted disease incorporates challenges from altered immunity associated with the underlying disease and its treatments. Considering the rarity of this malignancy, optimization of patient management requires multi-institutional collaboration. The Hairy Cell Leukemia Foundation (www.hairycellleukemia.org) was formed to coordinate these efforts. PMID:25110197

Grever, Michael R; Blachly, James S; Andritsos, Leslie A

2014-09-01

28

Hairy cell leukemia presenting initially with symptoms of Behçet's disease.  

PubMed

Vasculitis is relatively uncommon in lymphoproliferative disease and may predate the diagnosis of lymphoproliferative disease. Many vasculitides have been associated with hairy cell leukemia (HCL), including polyarteritis nodosa (PAN) and leukocytoclastic vasculitis. We herein report a case whose initial presentation was like Behçet's disease (BD) (arthritis, oral and genital ulcerations, papulopustular skin lesions) in addition to pancytopenia, but turned out to have HCL. Because of the overlap between their symptoms, like oral ulcerations, skin lesions, arthritis and constitutional findings, HCL and BD may mimic each other. We should keep in mind other reasons for vasculitis such as lymphoproliferative disease, especially whose who have hematological abnormalities such as pancytopenia. PMID:24762098

Oksuz, Mustafa Ferhat; Coskun, Belkis Nihan; Tufan, Ayse Nur; Orucoglu, Nurdan; Dalkilic, Ediz; Oztürk Nazl?o?lu, Hülya; Pehlivan, Yavuz

2014-07-01

29

Variant hairy cell leukemia following papillary urothelial neoplasm of bladder.  

PubMed

A 65 years old man was admitted with multiple lymphadenopathy, weight loss, night sweats and fatigue for 2 months. He had been treated for bladder cancer 2 years ago. Leukocyte count was 37.9 x10(9)/l. Peripheral blood smear had 91% lymphocytes. Lymphocytes had large nuclei with prominent nucleoli, heterogeneous appearance, and large cytoplasm with hairy projections. Flow cytometric immunophenotyping revealed CD20, CD22, CD24, CD45 and HLA-DR positivity. Atypical lymphocytes were stained with tartrate resistant acid phosphatase. Increased metabolic activity was detected in multiple lymph nodes, bone marrow and extremely enlarged spleen with positron emission tomography-computed tomography. Excisional biopsy of the left axillary lymph node revealed infiltration with diffuse B-cell leukemia/lymphoma. Immunohistochemistry showed CD20 positive atypical cells with weak expression of CD11c. The patient was diagnosed as a case of variant hairy cell leukemia and cladribine was administered. A probable second primary malignancy should be kept in mind in cases with a defined malignancy in the presence of unusual symptoms. PMID:24717996

Beyan, Cengiz; Kaptan, Kürsat

2014-03-01

30

Two cases of q-Fever in hairy cell leukemia.  

PubMed

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

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

2014-01-01

31

Cell Markers in Hairy Cell Leukemia Studied in Cells From 51 Patients  

Microsoft Academic Search

To determine the maturation arrest of the meoplastic cells of hairy-cell leukemia (HCL) and the spectrum of the surface markers om these cells. a series of 51 patients with this disease was studied. The cells of all but two of the patients showed momoclonal surface Ig with respect to light chains. In about one-third of the cases, only 'y heavy

Jan Jansen; Henrica R. E. Schuit; Chris J. L. M. Meijer; Janny A. van Nieuwkoop; Willy Hijmans

1982-01-01

32

Hairy Cell Leukemia Treatment: Where We Are Now?  

PubMed Central

Hairy cell leukemia (HCL) is a very rare type of leukemia, in which abnormal B lymphocytes, present in the bone marrow, spleen, and peripheral blood stream, get worse slowly or do not get worse at all. HCL is the disease where patients have pancytopenia with splenomegalia over 90% percent, palpable lymphadenopathy occur in 35% of patients, some form of serious infection eventually developed in over 50% of patients and was the most common cause of death in patients. HCL is dominantly a male disease, with the male-female ratio, ranging from 4:1 to 7:1. Treatment and prognosis of HCL depends on: the number of HC in the peripheral blood or bone marrow, if the spleen is enlarged and on the existence of the visible leukemia infection symptoms. Prognostic factors are similar to the above mentioned and also if the basic disease HCL is aggressive or the number of HC grow slowly and there is no need for treatment. Starting from September 1985 till September 2010, we observed a group with total number of 28 patients (22 males and 6 females) at the age of 30-76 (median range 46 years), all with HCL disease. From the total number of participants, 20 patients (71,43%) received hemotherapy, Cladribine and 8 patients (28,57%) received different type of therapy, such as immunomodulator therapy, surgery or combination of both, without Cladribine. Most effective therapy for HCL, from all of the above mentioned was definitely Cladribine which is dominant with a resulting response rates of 80-100%, where 70-90% of patients were achieving a complete remission, as defined by a complete disappearance of hairy cells in the bone marrow. PMID:23678301

Krstevska, Svetlana; Genadieva-Stavric, Sonja; Sotirova, Tatjana; Spasovski, Dejan; Balkanov, Trajan

2011-01-01

33

Treatment of refractory hairy cell leukemia with a BRAF-inhibitor: lessons to be learnt.  

PubMed

Hairy cell leukemia is a rare chronic lymphoproliferative disorder with indolent but progressive clinical course. Patients require treatment when they have significant cytopenia or recurrent infections. The gold standard treatment are purine nucleoside analogues (cladribine and pentostatine), with these agents the rate of complete remission can approach even 95 %. The differential diagnosis between classical hairy cell leukemia and other, rare splenic lymphomas that can mimic this disease might be really challenging. Splenic lymphoma with villous lymphocytes and other new, provisional WHO entities share some, but not all immunophenotypical features with hairy cell leukemia. The correct diagnosis is of an extreme importance as these entities require different treatment. Thus further investigation in the pathogenesis of hairy cell leukemia is required in order to solve this challenge. Discovery of the BRAF V600E mutation as a disease-defining genetic event in hairy cell leukemia can be helpful in both differential diagnosis and treatment of this disease. We report the case of three hairy cell leukemia patients, whose diagnosis or treatment was based on this newly discovered somatic mutation, but the treatment results and side effects were individual. PMID:24789721

Sári, Eszter; Nagy, Zsolt György; Baghy, Kornélia; Rajnai, Hajnalka; Bödör, Csaba; Csomor, Judit; Barna, Gábor; Rudas, Gábor; Kovalszky, Ilona; Demeter, Judit

2014-10-01

34

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

PubMed

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

35

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

36

Interferons Regulate the in vitro Differentiation of Multilineage Lympho-Myeloid Stem Cells in Hairy Cell Leukemia  

Microsoft Academic Search

In vitro 14-day cultures of peripheral blood mononuclear cells from hairy cell leukemia patients consistently showed the presence of hematopoietic stem cells giving rise to multilineage colonies containing a high proportion of lymphoid cells associated with the myeloid and erythroid progenitors. These stem cells are not the hairy cells but appear to be pluripotent lymphomyeloid primitive stem cells persisting in

Rita Michalevicz; Michel Revel

1987-01-01

37

Heterogeneous somatic hypermutation status confounds the cell of origin in hairy cell leukemia  

Microsoft Academic Search

Hairy cell leukemia (HCL) is thought to arise from a post-germinal center (GC) B-cell, however the exact normal counterpart remains unclear. We performed VH gene analysis of 32 HCL cases, revealing somatically mutated VH genes (<98% homology) in 27 cases and unmutated VH genes in five cases, four of which displayed germline VH genes. Intraclonal heterogeneity was evident in the

Mia Thorsélius; Sarah H. Walsh; Ulf Thunberg; Hans Hagberg; Christer Sundström; Richard Rosenquist

2005-01-01

38

Hairy cell leukemia: A B-lymphocytic disorder derived from splenic marginal zone lymphocytes?  

Microsoft Academic Search

Although there is increasing evidence that the majority of cases of hairy cell leukemia represent B-lymphoproliferative disorders, the exact subset of B-cells from which hairy cells are derived, is still unclear. On the basis of results obtained in previous studies, and data collected from the literature, it is suggested that B-lymphocytes normally residing in the marginal zone of the splenic

J. J. van den Oord; C. de Wolf-Peeters; V. J. Desmet

1985-01-01

39

Decreased NK activity in hairy cell leukemia (HCL): An analysis at the cellular level  

Microsoft Academic Search

Peripheral blood lymphocytes (PBL) of eleven patients with Hairy Cell Leukemia were studied for surface phenotype and for NK activity against the K 562 cell line (using both the standard 51Cr Release Assay and the Single Cell Cytotoxicity Assay on poly-L-lysine coated coverslips). A significant reduction in NK activity, target binding cells (TBC) and NK active cells (NKa) was detected.

L. Fontana; G. De Rossi; G. De Sanctis; F. Ensoli; M. Lopez; L. Annino; F. Mandelli

1986-01-01

40

Hairy cell leukemia: at the crossroad of somatic mutation and isotype switch  

Microsoft Academic Search

Hairy cell leukemia (HCL) commonly ex- presses multiple immunoglobulin iso- types, a feature rare in other B-cell malig- nancies or in normal B cells. In HCL, there is no phenotypic evidence for subpopula- tions, and single cells from one previous case contained transcripts for several isotypes. This raises the questions of the differentiation status of the cell of origin and

Francesco Forconi; Surinder S. Sahota; Donatella Raspadori; Micaela Ippoliti; Gavin Babbage; Francesco Lauria; Freda K. Stevenson

2004-01-01

41

High Response Rate of Hairy Cell Leukemia Patients to Immunotoxin Treatment Raises Hopes  

Cancer.gov

An ongoing phase I clinical trial at the National Cancer Institute reports that 11 of 16 patients with chemotherapy-resistant hairy cell leukemia (HCL), an uncommon form of B-cell cancer, had complete remissions lasting up to 18 months.

42

Platelet-adjusted IFN dosage in the treatment of advanced hairy cell leukemia  

Microsoft Academic Search

It has been demonstrated that hairy cell leukemia (HCL) can be efficiently treated by various preparations of alpha interferons (IFN). Nevertheless, there are several open questions, such as the route, mode and dosage of IFN application. These variables of IFN treatment may be critical since a myelosuppressive effect of IFN, which is commonly seen in the initial phase of treatment,

F. Porzsolt; J. Thomä; M. Unsöld; W. Wolf; H. J. Obert; B. Kubanek; H. Heimpel

1985-01-01

43

Legionella longbeachae pneumonia in a patient splenectomized for hairy-cell leukemia  

Microsoft Academic Search

Summary A 63-year-old man was admitted to the respiratory intensive care unit for pneumonia. Fifteen years earlier, hairy cell leukemia had been diagnosed and the patient underwent splenectomy. A clinical suspicion of legionellosis, later confirmed by both serology and isolation of the microorganism, prompted initiation of high dose erythromycin intravenously. The patient steadily deteriorated and passed away eight days later.

Ruth Lang; Z. Wiler; J. Manor; R. Kazak; Ida Boldur

1990-01-01

44

Primary treatment of hairy cell leukemia: Should IFN-therapy replace splenectomy?  

Microsoft Academic Search

Hairy cell leukemia (HCL) was described first in 1958 by Bouroncle [2] in a patient who had the disease for more than 30 years. The disorder, initially named leukemic reticulo-endotheliosis is a distinct clinical-pathological entity. Important aspects of this disease have recently been published in two issues (Seminars in Oncology Dec. 1984) summarizing the results of a workshop held at

F. Porzsolt

1986-01-01

45

Development of hairy cell leukemia in familial platelet disorder with predisposition to acute myeloid leukemia.  

PubMed

Abstract Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) is an autosomal dominant disorder characterized by mild to moderate thrombocytopenia with or without its impaired function, inherited RUNX1 mutation and high incidence of myeloid malignancy, such as myelodysplastic syndrome or acute myeloid leukemia. A 72-year-old male visited our institute because of gradually progressive pancytopenia and splenomegaly, and was diagnosed as having hairy cell leukemia. He was administered one course of intravenous cladribine (0.12 mg/kg, day 1-5) and achieved hematological complete response. Mutation analyses of RUNX1 gene were underwent because familial history of hematological malignancies evoked a possibility of FPD/AML. As a result, RUNX1 L445P mutation was identified in the peripheral blood and the mutation was considered as germ-line mutation because the same mutation was detected in the buccal mucosa. BRAF V600E mutation was also identified in the peripheral blood but not in the buccal mucosa. To our knowledge, this is the first report of B cell malignancy arising from FPD/AML. PMID:23971860

Toya, Takashi; Yoshimi, Akihide; Morioka, Takehiko; Arai, Shunya; Ichikawa, Motoshi; Usuki, Kensuke; Kurokawa, Mineo

2014-01-01

46

Alpha-interferon induces remission in hairy cell leukemia without enhancement of natural killing  

Microsoft Academic Search

The number of large granular lymphocytes (LGL) and the capacity of peripheral blood mononuclear cells (PBMC) to lyse K 562 target cells in a natural killer (NK)-like fashion was evaluated in seven hairy cell leukemia (HCL) patients undergoing treatment with recombinant interferon-alpha-2 (rIFN-alpha-2). In HCL patients, whose peripheral blood showed high numbers (?15×103\\/µl) of leukemic cells the number of LGL

G. Gastl; W. Aulitzky; E. Leiter; R. Flener; C. Huber

1986-01-01

47

Constitutively activated Rho guanosine triphosphatases regulate the growth and morphology of hairy cell leukemia cells.  

PubMed

Hairy cell leukemia (HCL) is a rare type of chronic B-cell leukemia characterized by the hairy morphology of the leukemia cells. All of 5 HCL samples and an HCL-derived cell line, BNBH-I, showed serrated edges and hairlike projections in May-Grünwald Giemsa stain and protruding actin spikes and lamellipodia in phalloidin stain. These structures were hardly detected on B-cell chronic lymphocytic leukemia (B-CLL) and precursor B-cell acute lymphocytic leukemia (B-ALL) cells. Because Rho guanosine triphosphatases (GTPases) regulate the formation of these structures, we examined the expression levels and activation states of Rho GTPases in HCL cells. RhoA, Rac1, and Cdc42 were overexpressed and constitutively activated in HCL samples and BNBH-I cells but not in B-CLL or precursor B-ALL cells. Next we overexpressed dominant-negative (DN)-RhoA, DN-Rac1, and DN-Cdc42 in BNBH-I. As a result, each DN mutant repressed the growth of BNBH-I cells by more than 50% and inhibited actin spike formation, but only DN-Racl suppressed lamellipodia formation. We also found that enforced expression of constitutively active-RhoA, Rac, or Cdc42 in the proB-cell line Ba/F3 was sufficient to induce actin spike formation, whereas none of these molecules produced lamellipodia. These results indicated that constitutively activated Rho GTPases regulate the growth and unique morphology of HCL cells. PMID:12731670

Zhang, Xian; Machii, Takashi; Matsumura, Itaru; Ezoe, Sachiko; Kawasaki, Akira; Tanaka, Hirokazu; Ueda, Shuji; Sugahara, Hiroyuki; Shibayama, Hirohiko; Mizuki, Masao; Kanakura, Yuzuru

2003-04-01

48

p53 gene deletion and trisomy 12 in hairy cell leukemia and its variant  

Microsoft Academic Search

The deletion or mutation of the p53 tumour suppressor gene on chromosome 17p13 is known to be associated with aggressive disease in several B-cell malignancies. The present study describes the p53 gene status in 20 cases of hairy cell leukemia (HCL) and in 12 cases of its morphological variant (HCL-V) by fluorescsence in situ hybridization (FISH). A high incidence of

Kalliopi Vallianatou; Vasantha Brito-Babapulle; Estela Matutes; Shayne Atkinson; Daniel Catovsky

1999-01-01

49

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

50

Treatment of hairy-cell leukemia with chemoradiotherapy and identical-twin bone-marrow transplantation  

Microsoft Academic Search

A patient with progressive hairy-cell leukemia and a normal genetically identical twin presented an opportunity to determine the sensitivity of this disease to high-dose alkylating-agent chemotherapy and total-body irradiation, since the marrow aplasia induced could potentially be overcome by reconstitution with normal marrow stem cells from the twin. After such therapy the patient rapidly recovered normal marrow function with no

Martin A. Cheever; Alexander Fefer; Philip D. Greenberg; Frederick Appelbaum; James O. Armitage; C. Dean Buckner; G. E. Sale; Rainer Storb; Robert P. Witherspoon; E. Donnall Thomas

1982-01-01

51

a-Interferon Activates the Natural Killer System in Patients With Hairy Cell Leukemia  

Microsoft Academic Search

To elucidate the mechanisms of a-interferon's (a-INF) therapeutic effect on clinical and laboratory findings in hairy cell leukemia. we sequentially monitored different immunologic parameters in three patients treated with recombinant a-INF. The most evident effect of this treat- ment on the immune system was the recovery of natural killer (NK) cell in vitro activity of peripheral blood lympho- H AIRY

G. Semenzato; G. Pizzolo; C. Agostini; A. Ambrosetti; R. Zambello; L. Trentin; M. Luca; M. Masciarelli; M. Chilosi; F. Vinante; G. Perona; G. Cetto

1986-01-01

52

CD20dim-positive T-cell large granular lymphocytic leukemia in a patient with concurrent hairy cell leukemia and plasma cell myeloma  

PubMed Central

We report a CD20dim- positive T-cell large granular lymphocytic (T-LGL) leukemia in a patient with concurrent hairy cell leukemia and plasma cell myeloma. This patient was first diagnosed with T-LGL leukemia with dim CD20 expression, which by itself was a rare entity. He received no treatment for T-LGL leukemia. The patient later developed a hairy cell leukemia, which went into complete clinical remission after one cycle of 2-CdA. Five years later, he was diagnosed with a third malignancy, plasma cell myeloma. Complex cytogenetic aberrancies were present at the time when plasma cell myeloma was diagnosed. This is the first report, to the best of our knowledge, in the English literature with the aforementioned three distinct hematopoietic malignancies in one patient. PMID:21151394

Xu, Xiangdong; Broome, Elizabeth H; Rashidi, Hooman H; South, Sarah T; Dell'Aquila, Marie L; Wang, Huan-You

2010-01-01

53

Identification of hairy cell leukemia subset defining p35 as the human homologue of Ii  

Microsoft Academic Search

A molecule defining a subset of patients with hairy cell leukemia (HCL) on the basis of being abundantly labeled with [35S]methionine, was demonstrated to be the human homologue of murine Ii, a glycoprotein which lacks alloantigenic variation and is associated non-covalently with Ia antigens. In one-dimensional SDS-polyacrylamide gradient gel electrophoresis, the HCL-subset-defining molecule migrated with HLA-DR molecules which were immunoprecipitated

Robert C. Spiro; Takeshi Sairenji; Robert E. Humphreys

1984-01-01

54

Mechanism of Interferon Action in Hairy Cell Leukemia: A Model of Effective Cancer Biotherapy1  

Microsoft Academic Search

Hairy cell leukemia (HCL) is one of the few malignancies for which a-interferon (IFNa) is considered effective first-line therapy. However, the mechanisms of action of this agent in vivo have been the subject of much debate; in particular, the issue of whether clinical improvement in IFNa-treated HCL patients is dependent upon enhancement of host defenses or upon direct actions of

Suresh Vedantham; Haim Gamliel; Harvey M. Golomb

55

Hairy cell leukemia: an unusual lymphoproliferative disease. A study of 24 patients  

Microsoft Academic Search

A laboratory and clinical evaluation of 24 patients with hairy cell leukemia was carried out over a 23-month period. Most patients had splenomegaly without adenopathy or pancyotpenia. Nine of the patients had undergone splenectomy prior to referral; their median WBC count was 6600\\/mm³. The median WBC count for the 14 patients who had no prior therapy was 3550\\/mm³, and their

Harvey M. Golomb

1978-01-01

56

Disseminated ulcerating lupus panniculitis emerging under interferon therapy of hairy cell leukemia: treatment- or disease-related?  

PubMed

We report a 43-year-old woman, who underwent therapy with interferon-? for hairy cell leukemia. During interferon-? therapy she developed multiple subcutaneous swellings, accompanied by fever and fatigue. A skin biopsy revealed lobular, T-cell lymphocytic panniculitis. In conjunction with the clinical and immunological findings, the diagnosis of lupus panniculitis was made and interferon-? therapy stopped. Initially, she responded well to oral prednisone and hydroxychloroquine, but after several months she became resistant to it. Her condition worsened, she developed skin ulcers in the inflamed regions. Only with the leukemia-targeted therapy using cladribine and rituximab her skin condition could be controlled, suggesting hairy cell leukemia as an additional trigger of the lupus panniculitis. Our report is the first one to show induction of lupus panniculitis under interferon therapy of hairy cell leukemia and its presumable sustentation by the latter. PMID:24612373

Urosevic-Maiwald, Mirjana; Nobbe, Stephan; Kerl, Katrin; Benz, Rudolf

2014-04-01

57

Disseminated ulcerating lupus panniculitis emerging under interferon therapy of hairy cell leukemia: treatment or disease-related?  

PubMed

We report a 43-year old woman, who underwent therapy with interferon-? for hairy cell leukemia. During interferon-? therapy she developed multiple subcutaneous swellings, accompanied by fever and fatigue. A skin biopsy revealed lobular, T-cell lymphocytic panniculitis. In conjunction with the clinical and immunological findings the diagnosis of lupus panniculitis was made and interferon-? therapy stopped. Initially she responded well to oral prednisone and hydroxychloroquine, but after several months she became resistant to it. Her condition worsened and she developed skin ulcers in the inflamed regions. Only with leukemia-targeted therapy, using cladribine and rituximab, could her skin condition be controlled, suggesting hairy cell leukemia as an additional trigger of the lupus panniculitis. Our report is the first one to show induction of lupus panniculitis during interferon therapy of hairy cell leukemia and its presumable continued exacerbation by the latter. PMID:24656265

Urosevic-Maiwald, Mirjana; Nobbe, Stephan; Kerl, Katrin; Benz, Rudolf

2014-03-01

58

A CD5+ Leukemic Lymphoma with Monocytoid Features: An Unusual B-Cell Lymphoma Mimicking Hairy-Cell Leukemia  

Microsoft Academic Search

A case of lymphoma presenting with features shared by hairy cell leukemia (HCL) and its variant, intermediate lymphocytic lymphoma (ILL) and monocytoid B-cell lymphoma (MBCL) is described. Clinical presentation and the morphological findings observed in peripheral blood and in bone marrow biopsy suggested an HCL; however, the tartrate-resistant acid phosphatase negativity of peripheral blood lymphocytes, the histologic pattern observed in

Fausto Adami; Marco Chilos; Maurizio Lestani; Aldo Scarpa; Renato Zambello; Fabrizio Pomponi; Gianpietro Semenzato; Fabio Menestrina

1993-01-01

59

Response duration and recovery of CD4+ lymphocytes following deoxycoformycin in interferon-?-resistant hairy cell leukemia: 7-year follow-up  

Microsoft Academic Search

The long-term outcome of patients with hairy cell leukemia resistant to interferon-? (IFN- ?) following treatment with deoxycoformycin (DCF) was examined, and the kinetics of recovery of lymphocyte subsets and factors influencing the rate of recovery investigated. Between May 1986 and May 1989, 15 patients with histologically confirmed hairy cell leukemia resistant to IFN-? received DCF 4 mg\\/m2 every 2

JF Seymour; M Talpaz; R Kurzrock

1997-01-01

60

Long-term outcome of hairy cell leukemia treated with 2-chlorodeoxyadenosine  

Microsoft Academic Search

The long-term results of both pretreated and previously untreated patients with hairy cell leukemia (HCL) using uniformly\\u000a a single 7-day course of 2-chlorodeoxyadenosine (2-CdA) by continuous infusion are reported. In addition, the probability\\u000a of obtaining another response with this drug in patients who relapsed after 2-CdA treatment will be addressed. Forty-two consecutive\\u000a patients (32 men, 10 women) with a median

U. Jehn; R. Bartl; H. Dietzfelbinger; U. Vehling-Kaiser; B. Wolf-Hornung; W. Hill; V. Heinemann

1999-01-01

61

High levels of circulating soluble receptors for tumor necrosis factor in hairy cell leukemia and type B chronic lymphocytic leukemia.  

PubMed Central

The presence of soluble tumor necrosis factor (TNF) binding proteins (BP) was investigated in the sera of healthy volunteer blood donors and cancer patients. Two distinct types of TNFBP, types A and B, which are immunologically related to the cellular 75-kD TNF receptor (TNFR) and the cellular 55-kD TNFR, respectively, were assessed by immunoassays using nonblocking anti-receptor antibodies and 125I-recombinant human TNF alpha. As compared to the titers observed in 25 healthy controls, TNFBP types A and B titers were found to be elevated in almost all sera obtained from patients with underlying malignant disease. The highest amounts of TNFBP were seen in the sera of patients with B cell malignancies including hairy cell leukemia (HCL) and type B chronic lymphocytic leukemia. Treatment of HCL patients with recombinant human interferon-alpha was associated with decrease of circulating TNFBP. PMID:1314854

Digel, W; Porzsolt, F; Schmid, M; Herrmann, F; Lesslauer, W; Brockhaus, M

1992-01-01

62

Co-existence of cutaneous T-cell lymphoma and B hairy cell leukemia.  

PubMed

A primary cutaneous form of peripheral T-cell lymphoma (PTCL) and a low grade B-cell non-Hodgkin's lymphoma that was classified as a variant of hairy cell leukemia (HCL) were simultaneously diagnosed in a 79-year-old woman by both phenotypic and genotypic analyses. The coexistence of a T- and B-cell lymphoma in the same patient is rare, and, to our knowledge, this particular association has not been previously described. The patient was referred to our Department for evaluation of multiple cutaneous itchy, reddish plaques; laboratory analyses disclosed a lymphocytosis, that presented 6 years earlier. A bone marrow aspirate showed a 50% B-cell interstitial infiltrate, while a skin biopsy surprisingly revealed a PTCL. Clonality of both neoplastic processes was assessed by Southern blot analysis. The indolent clinical course of the cutaneous disease, and the low and stable number of circulating neoplastic T cells supported the diagnosis of a mycosis fungoides (MF)-like PTCL. Possible oncogenic events and/or putative underlying viral infections which could have played a role in the occurrence of B- and T-cell non-Hodgkin's lymphomas in the same patient are discussed. PMID:10861816

Paolini, R; Poletti, A; Ramazzina, E; Menin, C; Santacatterina, M; Montagna, M; Bonaldi, L; Del Mistro, A; Zamboni, S; D'Andrea, E

2000-07-01

63

Two new cases of familial hairy cell leukemia associated with HLA haplotypes A2, B7, Bw4, Bw6.  

PubMed

Hairy cell leukemia (HCL) is a rare hematological disorder of unknown origin. Thirteen familial cases of HCL have been reported, with 28 relatives affected. Here we report 2 cases of HCL in a family associated with HLA haplotypes A2, B7 and Bw4/6. PMID:15621808

Villemagne, Bruno; Bay, Jacques-Olivier; Tournilhac, Olivier; Chaleteix, Carine; Travade, Philippe

2005-02-01

64

Response to Splenectomy in 65 Patients With Hairy Cell Leukemia: An Evaluation of Spleen Weight and Bone Marrow Involvement  

Microsoft Academic Search

Sixty-five patients with hairy cell leukemia underwent splenectomy; 27 had a complete remission as defined by a return in WBC. RBC, and platelet counts to a defined level, and 38 had a partial remission with a return of only one or two of these parameters to the defined level. The 5-yr actuarial survival for all patients is 68%; for CR

Harvey M. Golomb; James W. Vardiman

65

Increased Incidence of Second Neoplasms in Patients Treated With Interferon a 2b for Hairy Cell Leukemia: A Clinicopathologic Assessment  

Microsoft Academic Search

We report that there is an unexpectedly high incidence of second neoplasms in patients after treatment of hairy cell leukemia (HCL) with interferon a 2b (IFN). In a cohort of 69 patients with HCL entered in a protocol using IFN as the primary treatment, and followed thereafter for a median of 91 months (range, 0.2 to 109 months), 13 patients

Patricia Kampmeier; Ricardo Spielberger; Jerome Dickstein; Rosemarie Mick; Harvey Golomb; James W. Vardiman

1994-01-01

66

Minimal Residual Disease May Predict Bone Marrow Relapse in Patients With Hairy Cell Leukemia Treated With 2-Chlorodeoxyadenosine  

Microsoft Academic Search

Minimal residual disease (MRD) can be detected in bone marrow core biopsies of patients with hairy cell leukemia (HCL) after treatment with 2-chlorodeoxyadenosine (2-CdA) using immunohistochemical (IHC) techniques. The purpose of this study was to determine whether the presence of MRD predicts bone marrow relapse. We studied paraffin- embedded bone marrow core biopsies from 39 patients with HCL in complete

Susan Wheaton; Martin S. Tallman; David Hakimian; LoAnn Peterson

1996-01-01

67

Treatment of Hairy Cell Leukemia With Recombinant Alpha Interferon: I. Quantitative Study of Bone Marrow Changes During the First Months of Treatment  

Microsoft Academic Search

Seventeen patients with hairy cell leukemia (HCL) were treated with low doses of recombinant alpha interferon (IFN) for over 4 months. Marked improvement was observed in peripheral blood and bone marrow in 1 5 of 17 patients. Comparison of pretreatment values and hemo- grams obtained after 4 months of treatment showed a marked decrease in circulating hairy cells (P <

Georges Flandrin; Sylvie Castaigne; Christian Billard; Michel Aguet; Michel Boiron; Ernesto Falcoff; Laurent Degos

1986-01-01

68

Hematopoietic stem cell origin of BRAFV600E mutations in hairy cell leukemia.  

PubMed

Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder characterized by somatic BRAFV600E mutations. The malignant cell in HCL has immunophenotypic features of a mature B cell, but no normal counterpart along the continuum of developing B lymphocytes has been delineated as the cell of origin. We find that the BRAFV600E mutation is present in hematopoietic stem cells (HSCs) in HCL patients, and that these patients exhibit marked alterations in hematopoietic stem/progenitor cell (HSPC) frequencies. Quantitative sequencing analysis revealed a mean BRAFV600E-mutant allele frequency of 4.97% in HSCs from HCL patients. Moreover, transplantation of BRAFV600E-mutant HSCs from an HCL patient into immunodeficient mice resulted in stable engraftment of BRAFV600E-mutant human hematopoietic cells, revealing the functional self-renewal capacity of HCL HSCs. Consistent with the human genetic data, expression of BRafV600E in murine HSPCs resulted in a lethal hematopoietic disorder characterized by splenomegaly, anemia, thrombocytopenia, increased circulating soluble CD25, and increased clonogenic capacity of B lineage cells-all classic features of human HCL. In contrast, restricting expression of BRafV600E to the mature B cell compartment did not result in disease. Treatment of HCL patients with vemurafenib, an inhibitor of mutated BRAF, resulted in normalization of HSPC frequencies and increased myeloid and erythroid output from HSPCs. These findings link the pathogenesis of HCL to somatic mutations that arise in HSPCs and further suggest that chronic lymphoid malignancies may be initiated by aberrant HSCs. PMID:24871132

Chung, Stephen S; Kim, Eunhee; Park, Jae H; Chung, Young Rock; Lito, Piro; Teruya-Feldstein, Julie; Hu, Wenhuo; Beguelin, Wendy; Monette, Sebastien; Duy, Cihangir; Rampal, Raajit; Telis, Leon; Patel, Minal; Kim, Min Kyung; Huberman, Kety; Bouvier, Nancy; Berger, Michael F; Melnick, Ari M; Rosen, Neal; Tallman, Martin S; Park, Christopher Y; Abdel-Wahab, Omar

2014-05-28

69

Serum Soluble Interleukin2 Receptor Is Associated With Clinical and Pathologic Disease Status in Hairy Cell Leukemia  

Microsoft Academic Search

AIRY CELL LEUKEMIA (HCL), a disease charac- H terized by splenomegaly without adenopathy, by pan- cytopenia, and by circulating malignant cells with prominent cytoplasmic projections requires therapy in most cases.'S2 The manifestations of HCL result from the combined effects of (a) leukemic infiltration of the red pulp of the spleen by hairy cells, which leads to hyper~plenism,~ and (b) leukemic

Jon M. Richards; Rosemarie Mick; Jill M. Latta; Karen Daly; Mark J. Ratain; James W. Vardiman; Harvey M. Golomb

1990-01-01

70

Phase 2 study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemia  

Microsoft Academic Search

Hairy cell leukemia (HCL) is an indolent B-cell neoplasm, strongly expressing CD20. Despite initial very high response rates following cladribine, many patients (pts) ultimately relapse. Having relapsed after prior treatment with cladribine, 24 HCL pts (21 male, 3 female) with a median age of 53.5 years were treated with ritux- imab at 375 mg\\/m2 intravenously weekly for 4 weeks. Of

Jorge Nieva; Kelly Bethel; Alan Saven

2003-01-01

71

Treatment with Low Dose Human Recombinant Interferon-Alpha-2ARG Induces Complete Remission in Patients with Hairy Cell Leukemia  

Microsoft Academic Search

Summary Five cases with advanced hairy cell leukemia refractory to treatment with splenectomy and chemotherapy as well as one patient presenting with a stage-A response to splenectomy were treated with rhu-IFN-?2-arg. 5 × 106 were administered intramuscularly every day. Both patients, with advanced disease resistant to conventional therapy and treated for six or more months with rhu-IFN-?2-arg, achieved complete clinical

G. Gastl; H. Denz; C. Abbrederis; J. Troppmair; J. Wiegele; D. Niederwieser; R. Flener; C. Huber

1985-01-01

72

An update: 12-year follow-up of patients with hairy cell leukemia following treatment with 2-chlorodeoxyadenosine  

Microsoft Academic Search

Long-term results of both pretreated and previously untreated patients (pts) with hairy cell leukemia (HCL) using uniformly a single 7-day course of 2-chlorodeoxyadenosine (2-CdA) by continuous infusion are reported. In addition, the probability of obtaining another response with this drug in pts who relapsed after 2-CdA treatment will be addressed. A total of 44 consecutive pts (34 males, 10 females)

U Jehn; R Bartl; H Dietzfelbinger; T Haferlach; V Heinemann

2004-01-01

73

Weekly administration of 2-chlorodeoxyadenosine in patients with hairy-cell leukemia is effective and reduces infectious complications  

Microsoft Academic Search

Background and Objective. It has been widely demon- strated that one single 7-day course continous infu- sion (c.i.) 2-chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg\\/kg daily is dramatically effective in induc- ing high and prolonged complete remission (CR) rates in patients with hairy-cell leukemia (HCL). How- ever, 2-CdA administration often results in severe neutropenia and lymphocytopenia both responsible for

FRANCESCO LAURIA; MONICA BOCCHIA; GIUSEPPE MAROTTA; DONATELLA RASPADORI; PIER LUIGI ZINZANI; DAMIANO RONDELLI

74

Long-term outcome with pentostatin treatment in hairy cell leukemia patients. A French retrospective study of 238 patients  

Microsoft Academic Search

With the introduction of new drugs such as alpha-interferon (IFN) and purine analogs, the management of hairy cell leukemia (HCL) patients has changed. However, deoxycoformycin (DCF) produced higher complete remission rates than IFN. The current study was undertaken to provide long-term data on duration of overall survival (OS) and disease-free survival (DFS) and incidence of subsequent malignancies. We retrospectively analyzed

F Maloisel; L Benboubker; M Gardembas; B Coiffier; M Divine; C Sebban; M Blanc; J-F Abgrall; P Lederlin; J-L Harousseau; A-M Blaise; B Grosbois; P Morice; C Ghandour; S Castaigne

2003-01-01

75

Update on the biology and treatment options for hairy cell leukemia.  

PubMed

Hairy cell leukemia (HCL) is an uncommon chronic leukemia of mature B cells. Leukemic B cells of HCL exhibit a characteristic morphology and immunophenotype and coexpress multiple clonally related immunoglobulin isotypes. Precise diagnosis and detailed workup is essential, because the clinical profile of HCL can closely mimic that of other chronic B-cell lymphoproliferative disorders that are treated differently. Variants of HCL, such as HCLv and VH4-34 molecular variant, vary in the immunophenotype and specific VH gene usage, and have been more resistant to available treatments. On the contrary, classic HCL is a highly curable disease. Most patients show an excellent long-term response to treatment with single-agent cladribine or pentostatin, with or without the addition of an anti-CD20 monoclonal antibody such as rituximab. However, approximately 30-40 % of patients with HCL relapse after therapy; this can be treated with the same purine analogue that was used for the initial treatment. Advanced molecular techniques have identified distinct molecular aberrations in the Raf/MEK-ERK pathway and BRAF (V600E) mutations that drive the proliferation and survival of HCL B cells. Currently, research in the field of HCL is focused on identifying novel therapeutic targets and potential agents that are safe and can universally cure the disease. Ongoing and planned clinical trials are assessing various treatment strategies, such as the combination of purine analogues and various anti-CD20 monoclonal antibodies, recombinant immunotoxins targeting CD22 (e.g., moxetumomab pasudotox), BRAF inhibitors, such as vemurafenib, and B-cell receptor signaling inhibitors, such as ibrutinib, which is a Bruton's tyrosine kinase inhibitor. This article provides an update of our current understanding of the pathophysiology of HCL and the treatment options available for patients with classic HCL. Discussion of variant forms of HCL is beyond the scope of this manuscript. PMID:24652320

Jain, Preetesh; Pemmaraju, Naveen; Ravandi, Farhad

2014-06-01

76

Unusual presentation of hairy cell leukemia: a case series of four clinically unsuspected cases.  

PubMed

Hairy cell leukemia (HCL) is characterized by pancytopenia and usually associated with massive splenomegaly, however the same may not be true in the clinical settings. Here we report four cases of HCL and all of them were without the classical clinical feature of splenomegaly. This is an observational study conducted between January 2013 to March 2014 where we could diagnose ten cases of HCL in Department of Hematology, All India Institute of Medical Sciences, New Delhi. Of these, four cases attracted attention because of absence of classical clinical features of HCL. Of the four cases, three presented with weakness/fatigability while fourth patient presented with recurrent respiratory tract infection. Surprising finding in these cases was absence of splenomegaly, both clinically and on imaging which demerit the suspicion of HCL clinically. All four had bi/pancytopenia and bone marrow examination coupled with immunophenotypic analysis confirmed the diagnosis of HCL. Three patients received chemotherapy with cladribine and achieved complete hematological remission. One patient did not receive chemotherapy due to poor general condition and was subsequently lost to follow up. To conclude, HCL can and do present without splenomegaly and this should not restrain one from suspecting HCL based on histomorphology which needs to be further confirmed by ancillary techniques. This finding in our series could be because these cases were picked early in their natural course of the disease. A high index of suspicion is essential for diagnosing and appropriately managing such cases. PMID:25332634

Venkatesan, S; Purohit, Abhishek; Aggarwal, Mukul; Manivannan, Prabhu; Tyagi, Seema; Mahapatra, Manoranjan; Pati, Hara P; Saxena, Renu

2014-09-01

77

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

78

Successful treatment of extranodal Hodgkin's lymphoma in a patient with longstanding hairy cell leukemia.  

PubMed

Purine analogs, particularly pentostatin and cladribine, are highly effective in hairy cell leukemia (HCL). Both of these drugs induce responses in approximately 80-95% of patients. However, it is not yet determined if treatment with these drugs can induce second malignancies. Hodgkin's lymphoma is very rare as a second malignancy and there are only 3 reported cases concerning the association of this lymphoma with HCL. We describe a patient with longstanding HCL in complete remission after cladribine, in whom extranodal Hodgkin's lymphoma appeared 8 years after the diagnosis of HCL. Magnetic resonance imaging revealed diffuse intra-osseal neoplastic infiltration of the corpora of the whole spinal column and extra-osseal propagation from the fifth thoracic vertebra into the spinal canal with spinal cord compression. Histological and immunohistochemical analysis of the extradural tumor, which was completely excised, disclosed nodular sclerosis Hodgkin's lymphoma with typical Reed-Sternberg cells that were positive for CD30, CD15, bcl-6, Ki67, p53, EBV LPM-1 and IgG, and negative for CD45, CD20, DBA44, kappa, lambda light chains and IgM. In addition, immunohistochemical analysis of the bone marrow in 1999 showed infiltration with positivity for IgM and negative for kappa light chains and IgG. These findings (expression of different immunoglobulins and light chains on the cells) suggest an independent origin of these 2 B-cell neoplasms. After neurosurgery the patient received 6 courses of the MP-ABVD protocol and achieved a complete remission, which has lasted 16 months thus far. PMID:16019516

Gotic, M; Cemerikic, V; Elezovic, I; Boskovic, D; Bila, J; Magic, Z; Jocic, D J; Pavlovic, D; Grujicic, D; Stosic, T; Wotherspoon, A; Catovsky, D

2005-05-01

79

De novo hairy cell leukemia with a major BCR/ABL1 rearrangement: a case report with a literature review.  

PubMed

Hairy cell leukemia (HCL) is a very rare mature B-cell neoplasm and its simultaneous occurrence with chronic myeloid leukemia has been reported in only three cases. The pathogenesis and relationship of the two diseases are not clear. Here we report a case of HCL expressing a BCR/ABL1 clone, which showed molecular remission of the fusion clones and achieved partial remission over nine months of cladribine therapy. After a thorough analysis of previous studies and the results of this patient, we speculate that a subclone evolved to have an additional genetic BCR/ABL1 rearrangement. We also review all published literature on HCL with BCR/ABL1 rearrangement and discuss the pathophysiology of these unusual cases. PMID:24698424

Won, Young-Woong; Kim, Sung Jong; Park, Tae Sung; Oh, Seung Hwan; Wan, Thomas S K; Baek, Eun Jung

2014-03-01

80

B-ly-7, a Monoclonal Antibody Reactive With Hairy Cell Leukemia, Also Defines an Activation Antigen on Normal CD8' T Cells  

Microsoft Academic Search

We undertook a study to determine the specificity of the monoclonal antibody, B-ly-7, for hairy cell leukemia (HCL) by examining the expression in 150 samples from B-cell lymphoproliferative diseases as well as screening for reac- tivity in a number of other hematologic malignancies. Within the B-cell lineage we found that the expression of B-ly-7 was highly specific for HCL and

Stephen P. Mulligan; Philippe Travade; Estella Matutes; Claire Dearden; Lydia Visser; Sibrand Poppema; Daniel Catovsky

1990-01-01

81

Long-term follow-up of remission duration, mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin  

Microsoft Academic Search

The nucleoside analogue, pentostatin, has demonstrated high complete response rates and long relapse-free survival times in patients with hairy cell leukemia, a disease that historically had been unre- sponsive to treatment. Long-term data on duration of overall survival and relapse- free survival and incidence of subse- quent malignancies with this agent are lacking. Patients completing the treat- ment phase of

Ian W. Flinn; Kenneth J. Kopecky; M. Kathryn Foucar; David Head; John M. Bennett; Robert Hutchison; William Corbett; Peter Cassileth; Thomas Habermann; Harvey Golomb; Kanti Rai; Elizabeth Eisenhauer; Frederick Appelbaum; Bruce Cheson; Michael R. Grever

2000-01-01

82

Restrictions upon Epstein-Barr virus infection of the leukemic cell are demonstrated in patients with hairy cell leukemia  

Microsoft Academic Search

We tested the hypothesis that Epstein-Barr virus (EBV) might actually infect leukemic hairy cells in vivo by examining those cells for the EBV-receptor, EBV nuclear antigen (EBNA) and membrane antigen (MA), for spontaneous transformation and rescue of infectious virus and for presence of EBV genome. EBV-receptors were found on subpopulations of leukemic cells from each of 7 patients with hairy

Takeshi Sairenji; Patricia S. Reisert; Robert Christopher Spiro; Carel Mulder; Robert E. Humphreys

1983-01-01

83

Hairy cell leukemia: proliferative response to B cell growth factor, its inhibition by recombinant interferons, and expression of interferon receptors  

SciTech Connect

The malignant B lumphocytes of hairy cell leukemia (HCL) patients are relatively unresponsive to the proliferative influences of standard B cell mitogens as determined by failure to incorporate /sup 3/H-thymidine into DNA. Using chromatographically-purified B cell growth factor (BCGF) proliferative stimulation of HCL cells by this factor was demonstrated. Proliferation was time-dependent and was detectable after 4-6 days of culture and increased up to 10 days of culture. This BCGF-mediated proliferation was completely abrogated by addition of 1000 U/ml alpha inteferon (IFN) at culture initiation, while gamma IFN did not reduce LCL cell proliferation. HCL cells demonstrated specific receptors for ..cap alpha../sub 2/ IGN using /sup 125/I-..cap alpha../sub 2/ IGN. Scatchard analysis estimated the number of type I IGN receptors at approximately 350 per cell, with a K/sub d/ of 7.1 x 10/sup -10/ M, indicating a high-affinity binding site for type I IFN on leukemic cells. The number of type I IFN receptors could be reduced or down-regulated by 18 hour incubation with 100 U/ml ..cap alpha.. or ..beta.. IFN. Similar decreases in binding of /sup 125/I-..cap alpha../sub 2/ IFN were found on cells removed from HCL patients 24 hours following their first treatment with IFN. When incubated in fresh medium, cells exposed to IFN in vivo were able to regenerate their IGN receptors, while those treated in vitro showed no increase in binding of /sup 125/I-..cap alpha../sub 2/ IFN after incubation. These data suggest that the in vitro effects of IFN on HCL cells parallel the in vivo effects and indicate that ..gamma..IFN is unlikely to be clinically active against HCL as ..cap alpha../sub 2/ IFN.

Paganelli, K.A.

1986-01-01

84

Concentrations of Organochlorines Related to Titers to Epstein-Barr Virus Early Antigen IgG as Risk Factors for Hairy Cell Leukemia  

Microsoft Academic Search

Hairy cell leukemia (HCL) is a rare chronic B-cell malignancy that, according to modern classifi- cations, 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

Marie Nordström; Lennart Hardell; Gunilla Lindström; Håkan Wingfors; Karin Hardell; Annika Linde

85

Hairy cell leukemia treated initially with purine analogs: a retrospective study of 107 patients from the Spanish Cooperative Group on Chronic Lymphocytic Leukemia (GELLC).  

PubMed

Abstract Purine analogs are highly effective in hairy cell leukemia (HCL) with response rates of 85%, but with many late relapses. We have retrospectively reviewed the clinical data from 107 patients treated with pentostatin (n = 27) or cladribine (n = 80), to investigate the long-term efficacy and to identify factors associated with the treatment-free interval (TFI). Complete remission and minimal residual disease (MRD) rates were similar in both groups. Median TFI was shorter (95 vs. 144 months) in the pentostatin group, although the difference was not significant (p = 0.476). MRD+ patients had shorter TFI than MRD- patients (97 months vs. not reached, p < 0.049). A hemoglobin level < 10 g/dL predicted for a shorter TFI only in the pentostatin group. Quality of response and number of hairy cells in the bone marrow are independent risk factors of treatment failure. The relationship between MRD+ and shorter TFI makes it of special interest to explore consolidation therapy with monoclonal antibodies to achieve durable responses. PMID:23885799

López Rubio, Montserrat; Da Silva, Carolina; Loscertales, Javier; Seri, Cristina; Baltasar, Patricia; Colado, Enrique; Pérez Fernández, Inmaculada; Osma, Mar; Gomis, Federico; González, Marcos; Jarque, Isidro; Vargas, Manuel; Monzó, Encarnación; Monteagudo, Dolores; Orts, Maria Isabel; Pardal, Emilia; Carbonell, Félix; Perez Calvo, Cesar; Garcia-Marco, Jose A

2014-05-01

86

Molecular Analysis of the Human Chromosome 5q13.3 Region in Patients with Hairy Cell Leukemia and Identification of Tumor Suppressor Gene Candidates  

Microsoft Academic Search

The pathogenesis of hairy cell leukemia (HCL) remains largely unknown since no specific genetic lesion has been identified in this disease. Previous cytogenetic analysis from our group has shown that chromosome abnormalities involving the 5q13 band are common in HCL, occurring in approximately 1\\/3 of patients. The data suggest that the 5q13.3 band is likely to harbor a gene involved

Xiushan Wu; Ganka Ivanova; Mats Merup; Monika Jansson; Birgitta Stellan; Dan Grandér; Eugene Zabarovsky; Gösta Gahrton; Stefan Einhorn

1999-01-01

87

Incidence of Response and Long-Term Follow-Up in Patients With Hairy Cell Leukemia Treated With Recombinant Interferon Alfa-2a  

Microsoft Academic Search

HE EFFICACY OF partially purified alfa interferon T (IFN-a) in patients with hairy cell leukemia (HCL) was first reported in 1984 by Quesada et a1.l Shortly thereafter, two recombinant preparations, rIFN-a2a (Rof- eron-A; Hoffmann-LaRoche Inc, Nutley, NJ) and rIFN-a2b (Intron-A; Schering Corp, Kenilworth, NJ), identical in structure except at amino acid 23, entered clinical trials in the United States and

Ellin Berman; Glenn Heller; Sanford Kempin; Timothy Gee; Ly-Le Tran; Bayard Clarkson

1990-01-01

88

Long-lasting complete remission in patients with hairy cell leukemia treated with 2-CdA: a 5-year survey  

Microsoft Academic Search

Between January 1991 and January 1994, 40 patients with hairy-cell leukemia (HCL), 30 males and 10 females, with a median age of 54 years, were treated with a single course of 2-chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg\\/kg\\/day continuous infusion for 7 days. Thirteen patients were untreated and 27 had previously received ? interferon. Thirty out of 40 patients

F Lauria; D Rondelli; PL Zinzani; M Bocchia; G Marotta; M Salvucci; D Raspadori; MA Ventura; S Birtolo; F Forconi; S Tura

1997-01-01

89

Hairy Cell Leukemia: A Retrospective Study of 235 Cases by the Italian Cooperative Group (ICGHCL) according to Jansen’s Clinical Staging System  

Microsoft Academic Search

This is a report from a cooperative study on hairy cell leukemia (HCL) involving 20 Hematology Departments in Italy. Data for the patients was collected between January 1967 and December 1981 and included 235 cases of which 203 could be evaluated; 160 were males (78.8%) and 43 females (21.2%) with an M:F ratio of about 3:1; mean age was 54

E. E. Damasio; M. Spriano; M. Repetto; A. R. Vimercati; E. Rossi; D. Occhini; A. M. Marmont

1984-01-01

90

Variant B cell receptor isotype functions differ in hairy cell leukemia with mutated BRAF and IGHV genes.  

PubMed

A functional B-cell receptor (BCR) is critical for survival of normal B-cells, but whether it plays a comparable role in B-cell malignancy is as yet not fully delineated. Typical Hairy Cell Leukemia (HCL) is a rare B-cell tumor, and unique in expressing multiple surface immunoglobulin (sIg) isotypes on individual tumor cells (mult-HCL), to raise questions as to their functional relevance. Typical mult-HCL also displays a mutated BRAF V(600)E lesion. Since wild type BRAF is a primary conduit for transducing normal BCR signals, as revealed by deletion modelling studies, it is as yet not apparent if mutated BRAF alters BCR signal transduction in mult-HCL. To address these questions, we examined BCR signalling in mult-HCL cases uniformly displaying mutated BRAF and IGHV genes. Two apparent functional sets were delineated by IgD co-expression. In sIgD(+ve) mult-HCL, IgD mediated persistent Ca(2+) flux, also evident via >1 sIgH isotype, linked to increased ERK activation and BCR endocytosis. In sIgD(-ve) mult-HCL however, BCR-mediated signals and downstream effects were restricted to a single sIgH isotype, with sIgM notably dysfunctional and remaining immobilised on the cell surface. These observations reveal discordance between expression and function of individual isotypes in mult-HCL. In dual sIgL expressing cases, only a single sIgL was fully functional. We examined effects of anti-BCR stimuli on mult-HCL survival ex-vivo. Significantly, all functional non-IgD isotypes increased ERK1/2 phosphorylation but triggered apoptosis of tumor cells, in both subsets. IgD stimuli, in marked contrast retained tumor viability. Despite mutant BRAF, BCR signals augment ERK1/2 phosphorylation, but isotype dictates functional downstream outcomes. In mult-HCL, sIgD retains a potential to transduce BCR signals for tumor survival in-vivo. The BCR in mult-HCL emerges as subject to complex regulation, with apparent conflicting signalling by individual isotypes when co-expressed with sIgD. This suggests the possibility that mutant BRAF by-passes BCR constraints in mult-HCL. PMID:24497953

Weston-Bell, Nicola J; Forconi, Francesco; Kluin-Nelemans, Hanneke C; Sahota, Surinder S

2014-01-01

91

Primary hairy cell leukemia/lymphoma of the breast: a case report and review of the literature.  

PubMed

Hairy cell leukemia/lymphoma (HCL) is a rare B-cell neoplasm primarily involving spleen, bone marrow, and blood. However, other sites of primary involvement do occur and can present a diagnostic and therapeutic challenge. We present an unusual case of HCL involving predominantly the breast that was diagnosed as an incidental finding during an elective reduction mammoplasty in an otherwise healthy asymptomatic woman. Bone marrow performed for staging revealed limited involvement by HCL. Notably, there was no splenomegaly and/or involvement of other extramedullary sites. The peripheral blood revealed minimal involvement detected by flow cytometry. Extensive immunohistochemical studies supported by positive BRAF V600E mutational status confirmed the diagnosis of HCL. The patient remains asymptomatic without treatment one year following the diagnosis. This is the first case of a well-documented HCL presenting primarily in the breast in an asymptomatic patient. We review the literature on extramedullary, extrasplenic involvement by HCL and discuss the diagnostic challenges as well as the utility of immunohistochemistry and molecular studies in the diagnosis of atypical presentations of HCL. PMID:25133005

Pilichowska, Monika; Shariftabrizi, Ahmad; Mukand-Cerro, Ian; Miller, Kenneth

2014-01-01

92

Primary Hairy Cell Leukemia/Lymphoma of the Breast: A Case Report and Review of the Literature  

PubMed Central

Hairy cell leukemia/lymphoma (HCL) is a rare B-cell neoplasm primarily involving spleen, bone marrow, and blood. However, other sites of primary involvement do occur and can present a diagnostic and therapeutic challenge. We present an unusual case of HCL involving predominantly the breast that was diagnosed as an incidental finding during an elective reduction mammoplasty in an otherwise healthy asymptomatic woman. Bone marrow performed for staging revealed limited involvement by HCL. Notably, there was no splenomegaly and/or involvement of other extramedullary sites. The peripheral blood revealed minimal involvement detected by flow cytometry. Extensive immunohistochemical studies supported by positive BRAF V600E mutational status confirmed the diagnosis of HCL. The patient remains asymptomatic without treatment one year following the diagnosis. This is the first case of a well-documented HCL presenting primarily in the breast in an asymptomatic patient. We review the literature on extramedullary, extrasplenic involvement by HCL and discuss the diagnostic challenges as well as the utility of immunohistochemistry and molecular studies in the diagnosis of atypical presentations of HCL. PMID:25133005

Pilichowska, Monika; Shariftabrizi, Ahmad; Miller, Kenneth

2014-01-01

93

Somatic mutation analysis of IgH variable regions reveals that tumor cells of most parafollicular (monocytoid) B-cell lymphoma, splenic marginal zone B-cell lymphoma, and some hairy cell leukemia are composed of memory B lymphocytes  

Microsoft Academic Search

The cell of origin of parafollicular (monocytoid) B cell lymphoma (PBCL), splenic marginal zone lymphoma (SMZL), and hairy cell leukemia (HCL) is controversial. To better understand the relationship between these low-grade B-cell neoplasms, we analyzed the nucleotide sequences of the rearranged immunoglobulin heavy (IgH) chain variable (V) region of the clonal population of cells in five cases of PBCL, four

Roberto N Miranda; John B Cousar; Richard D Hammer; Robert D Collins; Cindy L Vnencak-Jones

1999-01-01

94

Characterization of three hairy cell leukemia- derived cell lines (ESKOL, JOK-1, and Hair-M) by multiplex-FISH, comparative genomic hybridization, FISH, PRINS, and dideoxyPRINS  

Microsoft Academic Search

Hairy cell leukemia (HCL) is a chronic B-lymphocyte leukemia. Due to the proliferative inertia of the malignant cells, HCL-derived cell lines are an important tool for studies on this disease. We have elaborated the karyotypes of three HCL-derived cell lines, ESKOL, JOK-1, and Hair-M, by combining a range of molecular cytogenetic techniques, including multiplex (multicolor) fluorescence in situ hybridization (M-FISH),

C. Lindbjerg Andersen; M. Østergaard; B. Nielsen; B. Pedersen; J. Koch

2000-01-01

95

Indium 111-labeled platelet kinetic studies and platelet-associated IgG in hairy cell leukemia  

SciTech Connect

In order to study the pathogenesis of thrombocytopenia in patients with hairy cell leukemia (HCL), levels of platelet-associated IgG (PAIgG), platelet life span (MLS), and the sequestration site of autologous /sup 111/In-labeled platelets were measured in nine patients with HCL. Splenectomized patients (n = 4) had a higher platelet count (x = 122.5 X 10(9)/l; range, 80-190 X 10(9)/l) as well as higher levels of PAIgG (x = 10.7%; range, 5.8-16.9%), than nonsplenectomized patients (platelets x = 76 X 10(9)/l, range 40-100 X 10(9)/l; PAIgG x = 3.2%, range 2.2-4.2%). A normal recovery of /sup 111/In-labeled platelets was found in splenectomized patients, whereas a very low recovery was observed in the nonsplenectomized group (x = 70.2%, range, 50-82.5%, versus x = 22.4%, range, 15-28.2%). The MLS was borderline normal in all patients. The site of sequestration was the spleen in nonsplenectomized patients. The low recovery of /sup 111/In-labeled platelets in nonsplenectomized patients suggests hypersplenism with pooling as a major cause of thrombocytopenia, in addition to impaired thrombocytopoiesis and possible immune-mediated platelet destruction.

Panzer, S.; Lechner, K.; Neumann, E.; Meryn, S.; Haubenstock, A.

1986-07-15

96

Comparative expressed sequence hybridization studies of hairy cell leukemia show uniform expression profile and imprint of spleen signature.  

PubMed

Comparative expressed sequence hybridization (CESH) to chromosomes is a recently introduced technique that identifies chromosomal regions corresponding to a differential gene expression. This technique is analogous to comparative genomic hybridization (CGH) that detects genomic imbalances. We applied CESH for the study of hairy cell leukemia (HCL), a disorder with a largely unknown expression profile. Twelve HCL cases with spleen involvement were investigated by CESH and CGH. While the latter analysis identified only a few nonrecurrent genomic imbalances, CESH showed a consistent expression profile in all HCL cases. In addition, pairing normal spleen with normal lymph node, a "spleen signature" was established by CESH. This signature most likely reflects the expression profile of spleen-specific components, such as the sinusoidal lining cells from the red pulp and the marginal zone B cells from the white pulp. Imprint of the spleen signature was found in the HCL expression profile, suggesting that HCL may originate from a particular B-cell subset present in these splenic components. Besides pairing HCL with normal lymph node and spleen, we identified an "HCL signature" comprising several chromosome regions with altered expression. The most significantly underexpressed regions include 3p24, 3p21, 3q13.3-q22, 4p16, 11q23, 14q22-q24, 15q21-q22, 15q24-q25, and 17q22-q24; and 13q31 and Xq13.3-q21 were the most significantly overexpressed. These regions possibly harbor genes related to the biology and the pathogenesis of HCL. Their identification warrants further molecular investigations. PMID:15016649

Vanhentenrijk, Vera; De Wolf-Peeters, Chris; Wlodarska, Iwona

2004-07-01

97

Hairy cell: young living longer but not cured.  

PubMed

In this issue of Blood, Rosenberg et al provide a detailed retrospective description of the long-term outcome of young patients with a diagnosis of hairy cell leukemia treated with cladribine. PMID:24408202

Grever, Michael R

2014-01-01

98

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

99

BRAF V600E-Negative Hairy Cell Leukaemia  

PubMed Central

Since the initial report of the BRAF V600E mutation in hairy cell leukemia, numerous investigators have demonstrated the presence of this activating mutation in nearly all cases of this disease. A case of hairy cell leukemia is documented with a classical clinical, morphological, immunophenotypic, and cytochemical profile in which the BRAF V600E was not detected. The diagnostic and therapeutic implications are discussed. PMID:23653869

Langabeer, Stephen E.; O'Brien, David; McElligott, Anthony M.; Lavin, Michelle; Browne, Paul V.

2013-01-01

100

BRAF V600E-Negative Hairy Cell Leukaemia.  

PubMed

Since the initial report of the BRAF V600E mutation in hairy cell leukemia, numerous investigators have demonstrated the presence of this activating mutation in nearly all cases of this disease. A case of hairy cell leukemia is documented with a classical clinical, morphological, immunophenotypic, and cytochemical profile in which the BRAF V600E was not detected. The diagnostic and therapeutic implications are discussed. PMID:23653869

Langabeer, Stephen E; O'Brien, David; McElligott, Anthony M; Lavin, Michelle; Browne, Paul V

2013-01-01

101

The Monoclonal Antibodies aS-HCL 1 (aLeu-14) and aS-HCL 3 (aLeu-M5) Allow the Diagnosis of Hairy Cell Leukemia  

Microsoft Academic Search

To define cell surface antigens associated with hairy cell leukemia (HCL). and to gain better insight into the origin of this disease. we developed monoclonal antibodies against spleen cells of a patient with this disease. Although none of these antibodies alone proved specific for the leukemic cells. two of them. designated aS-HCL 1 (aLeu-14) and aS-HCL 3 (aLeu-M5) were found

Roland Schwarting; Harald Stein; Chang Yi

1985-01-01

102

Clinical characteristics and long-term outcome of young hairy cell leukemia patients treated with cladribine: a single-institution series.  

PubMed

Hairy cell leukemia (HCL) is a rare, indolent B-cell disorder in which single courses of cladribine induce high rates of complete responses. We report on 88 young HCL patients (?40 years of age at diagnosis) treated with cladribine from the Scripps Clinic HCL Database, of whom 83 were evaluable for response. Seventy-three patients (88%) achieved an initial complete response and 10 (12%) a partial response, with a median response duration of 57 months. Forty-eight patients (58%) relapsed, with a median time to first relapse for all responders of 54 months. Eight patients developed 11 second primary malignancies with an excess frequency of 1.60 (95% confidence interval, 0.80-2.89). Thirteen (15%) patients died with a mortality ratio compared with age-matched normals of 1.85 (95% confidence interval, 1.07-3.18). Median overall survival for all patients following the first cladribine course was 231 months, and 251 months from diagnosis. Single courses of cladribine induce high rates of complete and durable responses in the majority of young HCL patients and are therefore recommended for HCL patients regardless of age. PMID:24192579

Rosenberg, Joshua D; Burian, Carol; Waalen, Jill; Saven, Alan

2014-01-01

103

Immunohistochemical analysis using a BRAF V600E mutation specific antibody is highly sensitive and specific for the diagnosis of hairy cell leukemia.  

PubMed

Hairy cell leukemia (HCL) is usually diagnosed by morphology and flow cytometry studies. However, it is challenging sometimes to distinguish HCL from its mimics. Recently, the BRAF V600E mutation has been described as a disease-defining molecular marker for HCL which is present in nearly all cases of HCL but virtually absent in mimics of HCL. In this study, we investigated the possibility of using immunohistochemical detection of the BRAF V600E mutant protein to differentiate HCL from its mimics. A total of twenty-eight FFPE tissue specimens were studied, including HCL (n=12), HCL variant (HCL-v, n=3), splenic marginal zone lymphoma (SMZL, n=6), and other marginal zone lymphomas (MZL, n=7). Immunohistochemical studies were performed using a mouse monoclonal antibody (clone VE1, Spring Bioscience, CA) specific for BRAF V600E mutation. Molecularly confirmed BRAF V600E mutation positive and negative cases were used as the positive and negative controls respectively. All 12 cases of HCL showed cytoplasmic BRAF V600E protein expression in leukemia cells by immunohistochemical study regardless of tumor burden, whereas all cases of HCL mimics including HCL-v, SMZL, and MZL were negative for BRAF V600E protein. Using this BRAF V600E mutation specific antibody, this immunohistochemical study has 100% sensitivity and 100% specificity for the diagnosis of HCL in our cohort. In conclusion, immunohistochemical detection of the BRAF V600E mutant protein is highly sensitive and specific for the diagnosis of HCL. Compared to PCR or sequencing-based methodologies, immunohistochemistry is a relatively rapid and inexpensive alternative for the differential diagnosis between HCL and its mimics. PMID:25120816

Wang, Xuan J; Kim, Annette; Li, Shaoying

2014-01-01

104

Immunohistochemical Detection of Cyclin D1 Using Optimized Conditions Is Highly Specific for Mantle Cell Lymphoma and Hairy Cell Leukemia  

Microsoft Academic Search

Mantle cell lymphoma (MCL) is more aggressive when compared with other lymphomas composed of small, mature B lymphocytes. Cyclin D1 is overexpressed in MCL as a result of the translocation t(11;14)(q13;q32). Cyclin D1 immunohistochemistry in fixed, paraffin-embedded tissue contributes to the precise and reproducible diagnosis of MCL without the requirement of fresh tissue. However, its use in bone marrow biopsies

Roberto N. Miranda; Robert C. Briggs; Marsha C. Kinney; Pat A. Veno; Richard D. Hammer; John B. Cousar

2000-01-01

105

Basic Fibroblast Growth Factor Is Expressed by CD19\\/CD11c-Positive Cells in Hairy Cell Leukemia  

Microsoft Academic Search

12-o-tetradecanoyl-phorbol-13-acetate (TPA) plus calcium ionophore (Ca-Ip) led to an enhanced mRNA expression. Results of Western blot experiments showed that HC synthe- size at least three isoforms (approximately 18, 23, and 25 kD), but only the 23-kD isoform is exported. To assess the nature of the producer cell, double immunofluorescence analysis using a bFGF-specific and an anti-CD11c monoclonal anti- body (MoAb)

Gerhard Gruber; Josef D. Schwarzmeier; Medhat Shehata; Martin Hilgarth; Rudolf Berger

2010-01-01

106

Monoclonal antibody HBME-1 reacts with a minor subset of B cells with villous surface and can be useful in the diagnosis of hairy cell leukemia and other indolent lymphoproliferations of villous B lymphocytes.  

PubMed

The Hector Battifora mesothelial epitope-1 (HBME-1) monoclonal antibody has been generated against human mesothelioma cells and recognizes a biochemically unknown membrane epitope. We have accidentally found that the HBME-1 reacts with scattered lymphocytes showing villous surface in hyperplastic lymphoid tissue. To evaluate its reactivity pattern, we have performed a consecutive immunohistochemical study in nonneoplastic bone marrow and lymphoid samples (n = 40), as well as in malignant lymphoproliferations (n = 427), including hairy cell leukemia (HCL) (n = 72), HCL variant (HCL-v) (n = 13), splenic diffuse red pulp small B cell lymphoma (SDRPL) (n = 8), splenic B cell marginal zone lymphoma (SMZL) (n = 59), and splenic B cell lymphoma/leukemia, not further classifiable on bone marrow morphology (SBCL) (n = 37) cases. The staining pattern of HBME-1 was compared to DBA.44. HBME-1(+) villous lymphocytes were constantly detected in low number in nonneoplastic lymphoid tissues. With multicolor immunofluorescence staining, HBME-1(+) lymphocytes showed a CD20(+)/CD79a(+)/IgM(+) B cell phenotype. In B cell lymphoproliferations of villous lymphocytes, HBME-1 reactivity was demonstrated in 96 % of HCL, 39 % of HCL-v, 50 % of SDRPL, 12 % of SMZL, and 19 % of SBCL cases. Nodal and extranodal marginal zone lymphoma cases were positive in 12 % of the cases. A small minority (4 %) of the other B cell lymphomas and no T cell lymphoma revealed tumor cell reactivity with HBME-1. In conclusion, our study has established that HBME-1 reacts with a minor subset of B lymphocytes and a small proportion of B cell lymphomas, which has not been described previously. We suggest that HBME-1 can be a useful marker in the diagnosis of HCL and other indolent lymphoproliferations of villous B lymphocytes. PMID:24092261

Krenács, László; Tóth-Lipták, Judit; Demeter, Judit; Piukovics, Klára; Borbényi, Zita; Gogolák, Péter; Sári, Eszter; Bagdi, Enik?

2013-12-01

107

RhoGTPases and p53 Are Involved in the Morphological Appearance and Interferon-? Response of Hairy Cells  

PubMed Central

Hairy cell leukemia is an uncommon B-cell lymphoproliferative disease of unknown etiology in which tumor cells display characteristic microfilamentous membrane projections. Another striking feature of the disease is its exquisite sensitivity to interferon (IFN)-?. So far, none of the known IFN-? regulatory properties have explained IFN-? responsiveness nor have they taken into account the morphological characteristics of hairy cells. IFN-? profoundly alters cytoskeletal organization of hairy cells and causes reversion of the hairy appearance into a rounded morphology. Because cytoskeletal rearrangements are controlled by the Rho family of GTPases, we investigated the GTPase activation status in hairy cells and their regulation by IFN-?. Using immunolocalization techniques and biochemical assays, we demonstrate that hairy cells display high levels of active Cdc42 and Rac1 and that IFN-? down-regulates these activities. In sharp contrast, RhoA activity was low in hairy cells but was increased by IFN-? treatment. Finally, IFN-?-mediated morphological changes also implicated a p53-induced response. These observations shed light on the mechanism of action of IFN-? in hairy cell leukemia and are of potential relevance for the therapeutical applications of this cytokine. PMID:16436670

Chaigne-Delalande, Benjamin; Deuve, Lynda; Reuzeau, Edith; Basoni, Caroline; Lafarge, David; Varon, Christine; Tatin, Florence; Anies, Guerric; Garand, Richard; Kramer, Ijsbrand; Genot, Elisabeth

2006-01-01

108

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

2014-10-15

109

Plasma cell leukaemia masquerading as hairy cell leukaemia: a case report.  

PubMed

Plasma cell leukaemia is a rare and aggressive neoplasm with survival of less than one year with conventional treatment. It can rarely present with morphology mimicking hairy cell leukaemia. We present a case of plasma cell leukaemia with hairy cell morphology for its rarity, diagnostic difficulty and aggressive course. PMID:25332528

Kumar, Thota Narender; Krishnamani, Kalpathi; Gandhi, Linga Vijay; Sadashivudu, Gundeti; Raghunadharao, Digumarti

2014-09-01

110

Leukemia  

MedlinePLUS

... version of this page please turn Javascript on. Leukemia What Is Leukemia? Leukemia is a cancer of the blood cells. ... diagnosed with leukemia are over 50 years old. Leukemia Starts in Bone Marrow Click for more information ...

111

Alkaloid Formation in Hairy Roots and Cell Suspensions of Rauwolfia serpentina Benth  

Microsoft Academic Search

Growth and alkaloid formation of hairy roots of Rauwolfia serpentina and Rauwolfia vomitoria were compared with that of well established cell suspension cultures of Rauwolfia serpentina and differentiated plants. Cell suspensions revealed clearly better growth - twice of the dry weight observed for the root culture. The hairy roots do not produce the major indole alkaloids typical for the root

Heike Falkenhagen; Inna N. Kuzovkina; Irina E. Alterman; Lubov A. Nikolaeva; Joachim Stöckigt

1993-01-01

112

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

113

Integrated Human T-Cell Leukemia Virus H Genome in CD8 + T Cells From a Patient With \\  

Microsoft Academic Search

We previously reported isolation of human T-cell leukemia virus II (HTLV-Il) from a second patient (N.R.A.) with atypical hairy cell leukemia. Follow-up analysis of the characteristics of the patient's HTLV-ll infection over a 2-year period has revealed that the patient had two coexis- tant lymphoproliferative disorders. Oligoclonally integrated HTLV-lI was detected in DNA extracted from the patient's peripheral blood mononuclear

Joseph D. Rosenblatt; Janis V. Giorgi; David W. Golde; Jonathan Ben Ezra; Anna Wu; Carl D. Winberg; John Glaspy; William Wachsman; Irvin S. Y. Chen

1988-01-01

114

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

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; 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 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

2014-08-26

115

Leukemia -- Chronic T-Cell Lymphocytic  

MedlinePLUS

... Cell Lymphocytic : Overview Download PDF Leukemia - Chronic T-Cell Lymphocytic : Overview This section has been reviewed and ... Statistics › f t g e + Leukemia - Chronic T-Cell Lymphocytic Guide Cancer.Net Guide Leukemia - Chronic T- ...

116

Identification of uniquely expressed transcription factors in highly purified B-cell lymphoma samples  

E-print Network

), follicular lymphoma (FL), hairy cell leukemia (HCL), and mantle cell lymphoma (MCL). The identified lymphoid malignancies, for example, hairy cell leukemia (HCL) cannot easily be traced to a specific normal associated to the tumor cells of chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL

Peterson, Carsten

117

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, Jesus 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; Blade, Joan; Orlowski, Robert Z.; Shah, Jatin J.

2014-01-01

118

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

119

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. ...

120

Regulating the leukemia stem cell  

PubMed Central

Leukemia stem cells (LSCs) are responsible for sustaining and propagating malignant disease, and, as such, are promising targets for therapy. Studies of human LSCs have served an important role in defining the major tenets of the cancer stem cell model, which center on the frequencies of cancer stem cells, their potential hierarchical organization, and their degree of maturation. LSCs in acute myeloid leukemia (AML) have recently been studied using mouse syngeneic models of leukemia induced by MLL oncogenes. These studies have revealed that LSCs are more analogous to progenitor cells and employ embryonic stem cell-like genetic programs for their maintenance, prompting a refinement of the original cancer stem cell model with important implications for design of therapies to selectively target LSCs. PMID:19959097

Cleary, Michael L.

2009-01-01

121

Plasma cell leukemia: A case series from South India with emphasis on rarer variants.  

PubMed

Plasma cell leukemia (PCL) is a rare and aggressive variant of plasma cell dyscrasia. They occur de novo (primary) or as a late manifestation of multiple myeloma (secondary). Patients present with anemia, thrombocytopenia, renal failure, organomegaly and extramedullary manifestations. We are presenting this series as it is the second largest series from India (16) with 4 young cases (under 40 years of age), more number of female patients and two having 'hairy cell' morphology. It is recommended that techniques like immunophenotyping and protein electrophoresis be performed, whenever the morphology is not characteristic of plasma cells. PMID:25336792

Rajeswari, G; Paul, T Roshni; Uppin, Megha S; Uppin, Shantveer G; Rao, D Raghunadha; Raju D, D Sree Bhushan; Sadashindu, G

2014-07-01

122

Stress-Induced Mast Cell Activation in Glabrous and Hairy Skin  

PubMed Central

Mast cells play a key role in modulation of stress-induced cutaneous inflammation. In this study we investigate the impact of repeated exposure to stress on mast cell degranulation, in both hairy and glabrous skin. Adult male Wistar rats were randomly divided into four groups: Stress 1 day (n = 8), Stress 10 days (n = 7), Stress 21 days (n = 6), and Control (n = 8). Rats in the stress groups were subjected to 2?h/day restraint stress. Subsequently, glabrous and hairy skin samples from animals of all groups were collected to assess mast cell degranulation by histochemistry and transmission electron microscopy. The impact of stress on mast cell degranulation was different depending on the type of skin and duration of stress exposure. Short-term stress exposure induced an amplification of mast cell degranulation in hairy skin that was maintained after prolonged exposure to stress. In glabrous skin, even though acute stress exposure had a profound stimulating effect on mast cell degranulation, it diminished progressively with long-term exposure to stress. The results of our study reinforce the view that mast cells are active players in modulating skin responses to stress and contribute to further understanding of pathophysiological mechanisms involved in stress-induced initiation or exacerbation of cutaneous inflammatory processes. PMID:24904196

Caruntu, Constantin; Boda, Daniel; Musat, Sorin; Caruntu, Ana; Mandache, Eugen

2014-01-01

123

Targeting Leukemia Stem Cells and Stem Cell Pathways in ALL  

Microsoft Academic Search

\\u000a Growing evidence suggests that haematological malignancies are ­sustained by a critical population of leukemia-initiating\\u000a cells or leukemia stem cells. These cellular populations are likely to be the critical target for eradication of leukemia\\u000a and most likely form the reservoir for relapse and disease resistance. Leukemia stem cells (LSC) have been demonstrated in\\u000a Acute Lymphoblastic Leukemia (ALL), although their origins, identity

Clare Pridans; Brian J. P. Huntly

124

Immunotoxins for leukemia.  

PubMed

Unconjugated monoclonal antibodies that target hematopoietic differentiation antigens have been developed to treat hematologic malignancies. Although some of these have activity against chronic lymphocytic leukemia and hairy cell leukemia, in general, monoclonal antibodies have limited efficacy as single agents in the treatment of leukemia. To increase their potency, the binding domains of monoclonal antibodies can be attached to protein toxins. Such compounds, termed immunotoxins, are delivered to the interior of leukemia cells based on antibody specificity for cell surface target antigens. Recombinant immunotoxins have been shown to be highly cytotoxic to leukemic blasts in vitro, in xenograft model systems, and in early-phase clinical trials in humans. These agents will likely play an increasing role in the treatment of leukemia. PMID:24578503

Wayne, Alan S; Fitzgerald, David J; Kreitman, Robert J; Pastan, Ira

2014-04-17

125

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

126

Plumbagin modulates leukemia cell redox status.  

PubMed

Plumbagin is a plant naphtoquinone exerting anti-cancer properties including apoptotic cell death induction and generation of reactive oxygen species (ROS). The aim of this study was to elucidate parameters explaining the differential leukemia cell sensitivity towards this compound. Among several leukemia cell lines, U937 monocytic leukemia cells appeared more sensitive to plumbagin treatment in terms of cytotoxicity and level of apoptotic cell death compared to more resistant Raji Burkitt lymphoma cells. Moreover, U937 cells exhibited a ten-fold higher ROS production compared to Raji. Neither differential incorporation, nor efflux of plumbagin was detected. Pre-treatment with thiol-containing antioxidants prevented ROS production and subsequent induction of cell death by apoptosis whereas non-thiol-containing antioxidants remained ineffective in both cellular models. We conclude that the anticancer potential of plumbagin is driven by pro-oxidant activities related to the cellular thiolstat. PMID:25014531

Gaascht, François; Teiten, Marie-Hélène; Cerella, Claudia; Dicato, Mario; Bagrel, Denyse; Diederich, Marc

2014-01-01

127

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

ClinicalTrials.gov

Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; L1 Adult Acute Lymphoblastic Leukemia; L2 Adult Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

2014-11-03

128

Leukemia among participants in military maneuvers at a nuclear bomb test  

SciTech Connect

To test the possibility of a casual relationship between leukemia and exposure to nuclear radiation, the frequency of leukemia in personnel observing the detonation of a nuclear device called ''Smoky'' during August 1957 was determined. Of some 3224 men who witnessed the detonation, nine cases of leukemia were observed. They included four cases of acute myelocytic leukemia, three of chronic myelocytic leukemia, one of hairy cell lymphocyctic leukemia, and one of acute lymphocytic luekemia. These findings represent a significant increase over the expected leukemia incidence of 3.5 cases. Mean film-badge gamma radiation dose for the study group was 466.2 mrem. (17 references, 3 tables)

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

1980-10-03

129

Alternative BRAF mutations in BRAF V600E-negative hairy cell leukaemias.  

PubMed

The BRAF V600E mutation in exon 15 is considered the disease-defining mutation in hairy cell leukaemia (HCL), but single HCL cases lacking this mutation have been described. In 24 HCL, as well as in 194 various mature B- and T-cell neoplasms, we extended the search for BRAF mutations to exon 11. Two V600E-negative HCL contained novel, potentially functionally relevant mutations in exon 11 (F468C and D449E), while one other HCL was BRAF wild-type in exons 2-17. All non-HCL lymphomas lacked BRAF mutations. We therefore suggest screening of BRAF V600E-negative HCL for alternative exon 11 mutations in the diagnostic setting. PMID:24433452

Tschernitz, Sebastian; Flossbach, Lucia; Bonengel, Margrit; Roth, Sabine; Rosenwald, Andreas; Geissinger, Eva

2014-05-01

130

An immunophenotypic and molecular diagnosis of composite hairy cell leukaemia and chronic lymphocytic leukaemia.  

PubMed

Hairy cell leukaemia (HCL) and chronic lymphocytic leukaemia (CLL) are distinct clinicopathological B cell chronic lymphoproliferative disorders (B-CLPD). Both diseases have characteristic immunophenotypic and molecular features. The co-existence of two B-CLPD is perhaps more common than previously thought but a composite HCL and CLL has been rarely documented. A case is reported in which the morphology, integrated with an extensive immunophenotyping panel, and incorporation of the recently described HCL-associated BRAF V600E mutation, enabled the prompt diagnosis of composite HCL and CLL thus allowing appropriate treatment selection. This case serves to highlight the benefit of a multidisciplinary approach to the diagnosis of bi-clonal B-CLPD. PMID:23979856

Liptrot, Stuart; O' Brien, David; Langabeer, Stephen E; Quinn, Fiona; Mackarel, A Jill; Elder, Patrick; Vandenberghe, Elisabeth; Hayden, Patrick J

2013-12-01

131

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

132

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

133

Hairy Crabs  

E-print Network

Broadcast Transcript: So in Japan, the vending machines act alive: they talk to you and make recommendations. Here in China, the vending machines are not alive but their contents are. At a subway station in Nanjing, people can buy live hairy crabs...

Hacker, Randi

2011-02-16

134

Targeting Chronic Myeloid Leukemia Stem Cells  

Microsoft Academic Search

Chronic myeloid leukemia (CML) arises as a consequence of a chromosomal translocation giving rise to the Philadelphia chromosome\\u000a and Bcr-Abl oncogene. CML is a clonal disease of stem cell origin and an excellent example of a malignancy in which tumor-initiating\\u000a cells may hold the key to disease eradication. The known molecular basis of CML has enabled the development of Abl-specific

G. Vignir Helgason; Graham A. R. Young; Tessa L. Holyoake

2010-01-01

135

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

136

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

137

Long-term follow-up and second malignancies in 487 patients with hairy cell leukaemia.  

PubMed

A large, multicentre, retrospective survey of patients with hairy cell leukaemia (HCL) was conducted in France to determine the frequency of second malignancies and to analyse the long-term effects of the established purine nucleoside analogues (PNAs), cladribine and pentostatin. The survey retrospectively reviewed the medical history of patients and their immediate family, clinical and biological presentation at the time of HCL diagnosis, treatment choice, response to treatment, time to relapse and cause of death. Data were collected for 487 patients with HCL. Of the patients included in the survey, 18% (88/487) had a familial history of cancers, 8% (41/487) presented with malignancies before HCL diagnosis and 10% (48/487) developed second malignancies after HCL was diagnosed. An excess incidence of second malignancies was observed, with a standardized incidence ratio (SIR) of 1·86 (95% confidence interval (CI): 1·34-2·51), with no significant difference between PNAs. For second haematological malignancies alone, the SIR was markedly increased at 5·32 (95% CI: 2·90-8·92). This study highlights the high frequency of cancers in HCL patients and their family members. The frequency of second malignancies is notably increased, particularly for haematological malignancies. The respective role of pentostatin and cladribine in the development of second malignancies is debatable. PMID:24749839

Cornet, Edouard; Tomowiak, Cécile; Tanguy-Schmidt, Aline; Lepretre, Stéphane; Dupuis, Jehan; Feugier, Pierre; Devidas, Alain; Mariette, Clara; Leblond, Véronique; Thiéblemont, Catherine; Validire-Charpy, Patricia; Sutton, Laurent; Gyan, Emmanuel; Eisenmann, Jean-Claude; Cony-Makhoul, Pascale; Ysebaert, Loïc; Troussard, Xavier

2014-08-01

138

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

SciTech Connect

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, the authors 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.

Altman, R.; Harrich, D.; Garcia, J.A. (Univ. of California Los Angeles School of Medicine (USA)); Gaynor, R.B. (Univ. of California Los Angeles School of Medicine (USA) Wadsworth Veterans Hospital, Los Angeles, CA (USA))

1988-04-01

139

An autologous leukemia cell vaccine prevents murine acute leukemia relapse after cytarabine treatment.  

PubMed

Acute leukemias with adverse prognostic features carry a high relapse rate without allogeneic stem cell transplantation (allo-SCT). Allo-SCT has a high morbidity and is precluded for many patients because of advanced age or comorbidities. Postremission therapies with reduced toxicities are urgently needed. The murine acute leukemia model C1498 was used to study the efficacy of an intravenously administered vaccine consisting of irradiated leukemia cells loaded with the natural killer T (NKT)-cell agonist ?-galactosylceramide (?-GalCer). Prophylactically, the vaccine was highly effective at preventing leukemia development through the downstream activities of activated NKT cells, which were dependent on splenic langerin(+)CD8?(+) dendritic cells and which led to stimulation of antileukemia CD4(+) and CD8(+) T cells. However, hosts with established leukemia received no protective benefit from the vaccine, despite inducing NKT-cell activation. Established leukemia was associated with increases in regulatory T cells and myeloid-derived suppressor cells, and the leukemic cells themselves were highly suppressive in vitro. Although this suppressive environment impaired both effector arms of the immune response, CD4(+) T-cell responses were more severely affected. When cytarabine chemotherapy was administered prior to vaccination, all animals in remission posttherapy were protected against rechallenge with viable leukemia cells. PMID:25237205

Gibbins, John D; Ancelet, Lindsay R; Weinkove, Robert; Compton, Benjamin J; Painter, Gavin F; Petersen, Troels R; Hermans, Ian F

2014-11-01

140

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.

141

Flavaglines target primitive leukemia cells and enhance anti-leukemia drug activity.  

PubMed

Identification of agents that target human leukemia stem cells is an important consideration for the development of new therapies. The present study demonstrates that rocaglamide and silvestrol, closely related natural products from the flavagline class of compounds, are able to preferentially kill functionally defined leukemia stem cells, while sparing normal stem and progenitor cells. In addition to efficacy as single agents, flavaglines sensitize leukemia cells to several anticancer compounds, including front-line chemotherapeutic drugs used to treat leukemia patients. Mechanistic studies indicate that flavaglines strongly inhibit protein synthesis, leading to the reduction of short-lived antiapoptotic proteins. Notably though, treatment with flavaglines, alone or in combination with other drugs, yields a much stronger cytotoxic activity toward leukemia cells than the translational inhibitor temsirolimus. These results indicate that the underlying cell death mechanism of flavaglines is more complex than simply inhibiting general protein translation. Global gene expression profiling and cell biological assays identified Myc inhibition and the disruption of mitochondrial integrity to be features of flavaglines, which we propose contribute to their efficacy in targeting leukemia cells. Taken together, these findings indicate that rocaglamide and silvestrol are distinct from clinically available translational inhibitors and represent promising candidates for the treatment of leukemia. PMID:24577530

Callahan, K P; Minhajuddin, M; Corbett, C; Lagadinou, E D; Rossi, R M; Grose, V; Balys, M M; Pan, L; Jacob, S; Frontier, A; Grever, M R; Lucas, D M; Kinghorn, A D; Liesveld, J L; Becker, M W; Jordan, C T

2014-10-01

142

Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia  

Microsoft Academic Search

Targeting of cancer stem cells is believed to be essential for curative therapy of cancers, but supporting evidence is limited. Few selective target genes in cancer stem cells have been identified. Here we identify the arachidonate 5-lipoxygenase (5-LO) gene (Alox5) as a critical regulator for leukemia stem cells (LSCs) in BCR-ABL–induced chronic myeloid leukemia (CML). In the absence of Alox5,

Yaoyu Chen; Yiguo Hu; Haojian Zhang; Cong Peng; Shaoguang Li

2009-01-01

143

Cordycepin Regulates GSK-3?/?-Catenin Signaling in Human Leukemia Cells  

PubMed Central

Background Leukemia stem cells (LSCs) are a limitless cell source for the initiation and maintenance of leukemia. Activation of the Wnt/?-catenin pathway is required for the survival and development of LSCs. Therefore, targeting ?-catenin is considered a therapeutic strategy for the treatment of leukemia. The goal of this study was to explore whether cordycepin, an active component of the traditional medicine Cordyceps sinensis, regulates ?-catenin expression in leukemia cells. Methodology and Principal Findings In this study, we found that cordycepin significantly suppressed cell proliferation in all malignant cancer cells, including U937, K562, A549, HepG2, SK-Hep1 and MCF7 in a dose-dependent manner. However, cordycepin reduced ?-catenin levels in U937, K562 and THP1 leukemia cells and had no effect on other solid cancer cells. In addition, treatment with cordycepin significantly suppressed leukemia colony formation in soft agar assay. Cordycepin enhanced proteasome-dependent degradation and inhibited nuclear translocation of ?-catenin in leukemia cells. Cordycepin-reduced ?-catenin stability was restored by the addition of a pharmacological inhibitor of GSK-3?, indicating that cordycepin-suppressed ?-catenin stability is mediated by the activation of GSK-3?. Furthermore, cordycepin abolished the effect of Wnt3a-induced ?-catenin in leukemia cells. In addition, cordycepin-impaired ?-catenin is regulated by Akt activation but is not significantly influenced by AMPK or mTOR signal pathways. Significance Our findings show for the first time that codycepin selectively reduces ?-catenin stability in leukemia but not in other solid tumor cells. This suppressive effect is mediated by regulating GSK-3?. A synergistic combination of cordycepin with other treatments should be used as a novel strategy to eradicate leukemia via elimination of LSCs. PMID:24086728

Liu, Tzu-An; Tzean, Shean-Shong; Shen, Tang-Long; Liou, Jun-Yang

2013-01-01

144

Hairy strings  

SciTech Connect

Zero modes of the world-sheet spinors of a closed string can source higher order moments of the bulk supergravity fields. In this work, we analyze various configurations of closed strings focusing on the imprints of the quantized spinor vacuum expectation values onto the tails of bulk fields. We identify supersymmetric arrangements for which all multipole charges vanish; while for others, we find that one is left with Neveu-Schwarz-Neveu-Schwarz, and Ramond-Ramond dipole and quadrupole moments. Our analysis is exhaustive with respect to all the bosonic fields of the bulk and to all higher order moments. We comment on the relevance of these results to entropy computations of hairy black holes of a single charge or more, and to open/closed string duality.

Sahakian, Vatche [Keck Laboratory, Harvey Mudd College, Claremont, California 91711 (United States)

2006-01-15

145

Does hematopoietic stem cell transplantation benefit infants with acute leukemia?  

PubMed

A 6-month-old girl was diagnosed with acute lymphoblastic leukemia (ALL). She has completed induction therapy and is currently in first complete remission (CR1). You are asked by your resident if hematopoietic stem cell transplantation (HSCT) would benefit infants with acute leukemia. PMID:24319238

Sison, Edward Allan R; Brown, Patrick

2013-01-01

146

Gossypol-Induced Differentiation in Human Leukemia HL-60 Cells  

PubMed Central

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

2006-01-01

147

Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk 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; 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

2014-09-16

148

Infections in patients with leukemia and lymphoma.  

PubMed

Infectious complications remain a significant issue in the care of patients with hematologic malignancies. Inherent immune defects related to the primary disease process are present in patients with disorders such as chronic lymphocytic leukemia, multiple myeloma, hairy cell leukemia, and Hodgkin lymphoma. Therapy-related immunosuppression is also commonplace in these patients. This includes not only treatment-related neutropenia, but also defects in cell-mediated immunity, such as those that occur with purine analog therapy. In this chapter, we will review the pathogenesis of infection in these disorders, as well as the spectrum of infectious complications seen and suggested strategies for the prevention of infection. PMID:24706230

Morrison, Vicki A

2014-01-01

149

Leukemia  

MedlinePLUS

... embed/Ya8IzYwguVM?rel=0 SEER Stat Fact Sheets: Leukemia Expand All Collapse All Statistics at a Glance ... 5 Years Or More after Being Diagnosed with Leukemia? Relative survival statistics compare the survival of patients ...

150

Different roles of the mevalonate and methylerythritol phosphate pathways in cell growth and tanshinone production of Salvia miltiorrhiza hairy roots.  

PubMed

Salvia miltiorrhiza has been widely used in the treatment of coronary heart disease. Tanshinones, a group of diterpenoids are the main active ingredients in S. miltiorrhiza. Two biosynthetic pathways were involved in tanshinone biosynthesis in plants: the mevalonate (MVA) pathway in the cytosol and the methylerythritol phosphate (MEP) pathway in the plastids. The 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is the rate-limiting enzyme of the MVA pathway. The 1-deoxy-D-xylulose 5-phosphate synthase (DXS) and 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) are the key enzymes of the MEP pathway. In this study, to reveal roles of the MVA and the MEP pathways in cell growth and tanshinone production of S. miltiorrhiza hairy roots, specific inhibitors of the two pathways were used to perturb metabolic flux. The results showed that the MVA pathway inhibitor (mevinolin, MEV) was more powerful to inhibit the hairy root growth than the MEP pathway inhibitor (fosmidomycin, FOS). Both MEV and FOS could significantly inhibit tanshinone production, and FOS was more powerful than MEV. An inhibitor (D, L-glyceraldehyde, DLG) of IPP translocation strengthened the inhibitory effects of MEV and FOS on cell growth and tanshinone production. Application of MEV resulted in a significant increase of expression and activity of HMGR at 6 h, and a sharp decrease at 24 h. FOS treatment resulted in a significant increase of DXR and DXS expression and DXS activity at 6 h, and a sharp decrease at 24 h. Our results suggested that the MVA pathway played a major role in cell growth, while the MEP pathway was the main source of tanshinone biosynthesis. Both cell growth and tanshinone production could partially depend on the crosstalk between the two pathways. The inhibitor-mediated changes of tanshinone production were reflected in transcript and protein levels of genes of the MVA and MEP pathways. PMID:23209548

Yang, Dongfeng; Du, Xuhong; Liang, Xiao; Han, Ruilian; Liang, Zongsuo; Liu, Yan; Liu, Fenghua; Zhao, Jianjun

2012-01-01

151

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

ClinicalTrials.gov

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

2014-10-22

152

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

153

Inducement of specific CTLs by antigen-peptides from human leukemia cells and their cytotoxicity to leukemia cells  

Microsoft Academic Search

Summary  To investigate the inducement of cytotoxic T lymphocytes (CTLs) by antigen peptides mixture from different leukemia cells\\u000a and the cross-reaction of the mixtures from different cell lines, antigen peptides mixtures were prepared from different leukemia\\u000a cell lines respectively and then bound with Hsp70in vitro. Activation and proliferation of PBMC were observed after stimulation with different Hsp70-peptide complexes. The ratio of

Zuohua Feng; Guimei Zhang; Bo Huang; Dong Li; Hongtao Wang

2002-01-01

154

Correlation of the BRAF V600E mutation in hairy cell leukaemia with morphology, cytochemistry and immunophenotype.  

PubMed

Hairy cell leukaemia (HCL) has distinct clinical, morphological and immunophenotypic features with no recurrent cytogenetic or molecular abnormalities reported until the recent description of the BRAF V600E mutation in patients with classical HCL. The incidence of this mutation was sought in 27 patients with either classical HCL or HCL variant by an allele-specific PCR approach and findings related to morphology, cytochemistry and immunophenotype. A high degree of correlation was noted between the presence of BRAF V600E and established diagnostic criteria in 26/27 patients with HCL/HCL variant. Detection of the BRAF V600E mutation is therefore a useful adjunct in the differential diagnosis of HCL and HCL variant and highlights the value of a multifaceted approach to the diagnosis of this malignancy. PMID:22313586

Langabeer, S E; O'Brien, D; Liptrot, S; Flynn, C M; Hayden, P J; Conneally, E; Browne, P V; Vandenberghe, E

2012-08-01

155

Human T-cell leukemia viruses: epidemiology, biology, and pathogenesis.  

PubMed

The human T-cell lymphotropic viruses type I and type II are closely related human retroviruses that have similar biological properties, genetic organization and tropism for T lymphocytes. Along with the simian T-cell lymphoma virus type I, they define the group of retroviruses known as the primate T-cell leukemia/lymphoma viruses. Initially identified in 1980, the human T-cell lymphotropic virus type I has been implicated as the etiologic agent of adult T-cell leukemia/lymphoma and of a degenerative neurologic disorder known as tropical spastic paraparesis or human T-cell lymphotropic virus type I-associated myelopathy. The intriguing link between human T-cell lymphotropic virus type, T-cell malignancy, and a totally unrelated and non-overlapping neurological disorder suggests divergent and unique pathogenetic mechanisms. This review will address the epidemiology, molecular biology, and pathogenesis of human T-cell leukemia viruses. PMID:9242992

Ferreira, O C; Planelles, V; Rosenblatt, J D

1997-06-01

156

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 Araujo; de Melo, Ricardo Pereira; Napimoga, Marcelo Henrique; Laguna-Abreu, Maria Theresa Ceravolo

2011-01-01

157

Expression of tie receptor tyrosine kinase in leukemia cell lines.  

PubMed

The tie receptor tyrosine kinase mRNA was originally identified as an amplified product in reverse transcription-polymerase chain reaction analysis of human K562 leukemia cell RNA. In situ hybridization analysis revealed that the corresponding mouse gene is expressed predominantly in endothelial cells. We have explored tie mRNA and protein expression in tumor cell lines. The 4.4 kb tie mRNA was expressed at high levels in five of five human megakaryoblastic leukemia cell lines studied and in two IL-3-dependent mouse myeloid leukemia cell lines, but not in 42 other leukemia cell lines representing various hematopoietic lineages. Increased expression of tie mRNA and protein was observed upon treatment of the megakaryoblastic leukemia cells with the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA), known to enhance megakaryoblastic markers. Among several cell lines from solid tumors, two fibrosarcomas, one rhabdomyosarcoma and one melanoma cell line were positive for tie mRNA. These results suggest that among hematopoietic lineages tie is predominantly expressed in cells with megakaryoblastic properties and that the tie tyrosine kinase is a receptor for a regulatory factor specific for megakaryoblasts, endothelial cells, and occasional tumor cell lines derived from mesenchymal tissues. PMID:8412320

Armstrong, E; Korhonen, J; Silvennoinen, O; Cleveland, J L; Lieberman, M A; Alitalo, R

1993-10-01

158

Higher hairy graph homology.  

E-print Network

We study the hairy graph homology of a cyclic operad; in particular we show how to assemble corresponding hairy graph cohomology classes to form cocycles for ordinary graph homology, as defined by Kontsevich. We identify the part of hairy graph homology coming from graphs with cyclic fundamental group as the dihedral homology of a related associative algebra with involution. For the operads Comm, Assoc and Lie we compute this algebra explicitly, enabling us to apply known results on dihedral homology to the computation of hairy graph homology. In addition we determine the image in hairy graph homology of the trace map defined in [CKV], as a symplectic representation. For the operad Lie assembling hairy graph cohomology classes yields all known non-trivial rational homology of Out(F_n). The hairy graph homology of Lie is also useful for constructing elements of the cokernel of the Johnson homomomorphism of a once-punctured surface.

Jim Conant; Martin Kassabov; Karen Vogtmann

159

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

Federal Register 2010, 2011, 2012, 2013

...service organizations, including Vietnam Veterans of America, Inc...exposure to the herbicides used in Vietnam and the occurrence of specific...including, but not limited to, dioxin. This rulemaking, however...operations in the Republic of Vietnam during the period...

2010-08-31

160

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

Federal Register 2010, 2011, 2012, 2013

...support of military operations in the Republic of Vietnam during the Vietnam era and each disease suspected to be associated with...exposed to herbicides during service in the Republic of Vietnam during the Vietnam era; and (3) whether...

2010-03-25

161

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 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; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

2014-04-25

162

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

163

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.; Falcao, Roberto P.; Pintao, Maria-Carolina; McCoy, J. Philip; Rizzatti, Edgar Gil; Young, Neal S.

2007-01-01

164

Mitochondrial DNAsequence variation in single cells from leukemia patients  

Microsoft Academic Search

cells, in patients compared to controls. Patients with similar clinical leukemia types, particularly acute myeloid leuke- mia (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

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

2007-01-01

165

RNA viral vectors for improved Agrobacterium-mediated transient expression of heterologous proteins in Nicotiana benthamiana cell suspensions and hairy roots  

PubMed Central

Background Plant cell suspensions and hairy root cultures represent scalable protein expression platforms. Low protein product titers have thus far limited the application of transient protein expression in these hosts. The objective of this work was to overcome this limitation by harnessing A. tumefaciens to deliver replicating and non-replicating RNA viral vectors in plant tissue co-cultures. Results Replicating vectors derived from Potato virus X (PVX) and Tobacco rattle virus (TRV) were modified to contain the reporter gene ?-glucuronidase (GUS) with a plant intron to prevent bacterial expression. In cell suspensions, a minimal PVX vector retaining only the viral RNA polymerase gene yielded 6.6-fold more GUS than an analogous full-length PVX vector. Transient co-expression of the minimal PVX vector with P19 of Tomato bushy stunt virus or HC-Pro of Tobacco etch virus to suppress post-transcriptional gene silencing increased GUS expression by 44 and 83%, respectively. A non-replicating vector containing a leader sequence from Cowpea mosaic virus (CPMV-HT) modified for enhanced translation led to 70% higher transient GUS expression than a control treatment. In hairy roots, a TRV vector capable of systemic movement increased GUS accumulation by 150-fold relative to the analogous PVX vector. Histochemical staining for GUS in TRV-infected hairy roots revealed the capacity for achieving even higher productivity per unit biomass. Conclusions For the first time, replicating PVX vectors and a non-replicating CPMV-HT vector were successfully applied toward transient heterologous protein expression in cell suspensions. A replicating TRV vector achieved transient GUS expression levels in hairy roots more than an order of magnitude higher than the highest level previously reported with a viral vector delivered by A. tumefaciens. PMID:22559055

2012-01-01

166

Leukemia  

MedlinePLUS Videos and Cool Tools

... 27,000 adults and more than 2,000 children in the United States are diagnosed with leukemia ... effects of radiotherapy may be long lasting. Young children who receive radiation to the brain may develop ...

167

The characterization and role of leukemia cell-derived dendritic cells in immunotherapy for leukemic diseases  

PubMed Central

Summary Usually, an effective anti-leukemia immune response cannot be initiated effectively in patients with leukemia. This is probably related to immunosuppression due to chemotherapy, down-regulation of major histocompatibility complex (MHC) II molecules, and the lack of co-stimulatory molecules on dendritic cells (DC). In light of this problem, some methods had been used to induce leukemia cells to differentiate into mature DCs, causing them to present leukemia-associated antigens and activating naïve T cells. Furthermore, leukemia-derived DCs could be modified with tumor antigens or tumor-associated antigens to provide a new approach to anti-leukemia therapy. Numerous studies have indicated factors related to the induction and functioning of leukemia-derived DCs and the activation of cytotoxic T-lymphocytes (CTLs). These include the amount of purified DCs, cytokine profiles appropriate for inducing leukemia-derived DCs, effective methods of activating CTLs, reasonable approaches to DC vaccines, and the standardization of their clinical use. Determining these factors could lead to more effective leukemia treatment and benefit both mankind and scientific development. What follows in a review of advances in and practices of inducing leukemia-derived DCs and the feasibility of their clinical use.

Yuan, Changjin; Song, Guanhua; Jiang, Guosheng

2012-01-01

168

Leukemia stem cells in 2010: current understanding and future directions.  

PubMed

Myeloid leukemias are clonal disorders originating in a primitive multipotential hematopoietic cell and characterized by aberrant proliferation, differentiation and maturation of leukemic progenitors and precursor cells. These diseases are the result of multiple genetic and epigenetic events, although the nature and number of events vary widely among patients. For over four decades, studies have identified sub-populations of leukemic cells possessing different functional capabilities. Investigators have struggled to understand the origin and significance of this heterogeneity. The stem cell model for myeloid malignancies has offered one potential explanation. Since 1994, experimental data supporting the presence of leukemia stem cells has been reported and validated in numerous studies. We will review the history of the model, data from the past decade supporting the stem cell model for myeloid malignancies, more recent data regarding patient specific variability in leukemic stem cell surface antigen phenotype and the impact the stem cell model has on the care of patients with myeloid malignancies. PMID:21216511

Becker, Michael W; Jordan, Craig T

2011-03-01

169

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

170

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.

171

Characterization of T Cells Immortalized by Taxl of Human T-cell Leukemia Virus Type 1  

Microsoft Academic Search

UMAN T-CELL leukemia virus type 1 (HTLV-l) is etiologically associated with adult T-cell leukemia (ATL) and tropical spastic paraparesis (TSP)\\/HTLV-1 -as- sociated myelopathy (HAM).'.' This virus characteristically has the ability to immortalize normal T cells in vitro.',' HTLV-l-immortalized T cells differ in many ways from normal T cells. The interleukin-2 (IL-2) requirement for cell growth is decreased in many HTLV-1-immortalized

Tsuyoshi Akagi; Hiroaki Ono; Kunitada Shimotohno

1995-01-01

172

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

2014-04-25

173

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

174

Constitutive activation of transcription factor AP1 in primary adult T-cell leukemia cells  

Microsoft Academic Search

Human T-cell leukemia virus type-I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL). This study exam- ined the status of the oncogenic transcrip- tion factor AP-1 in leukemic cells freshly isolated from patients with ATL. Leuke- mic cells from peripheral blood of all patients with ATL exhibited constitutive AP-1 DNA binding activity, whereas mono- nuclear cells from normal

Naoki Mori; Masahiro Fujii; Kousuke Iwai; Shuichi Ikeda; Yoshihiro Yamasaki; Tomoko Hata; Yasuaki Yamada; Yuetsu Tanaka; Masao Tomonaga; Naoki Yamamoto

2000-01-01

175

Ipilimumab in Treating Patients With Relapsed Hematologic Malignancies After Donor Stem Cell Transplant  

ClinicalTrials.gov

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; Chronic Myelomonocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; 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; Progressive Hairy Cell Leukemia, Initial Treatment; 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; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

2014-11-07

176

Treating Adult T-cell Leukemia/Lymphoma  

Cancer.gov

In this clinical trial, researchers will use denileukin diftitox (Ontak), a genetically engineered protein that combines segments of interleukin-2 and diphtheria toxin, to treat patients with adult T cell leukemia/lymphoma that shows a receptor protein for interleukin-2.

177

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

178

[Molecular-targeted therapies against adult T-cell leukemia].  

PubMed

Adult T-cell leukemia(ATL) is caused by infection with a human retrovirus, human T-cell leukemia virus type 1(HTLV-1). Since replication of HTLV-1 is generally suppressed in vivo, antiviral drugs targeting HTLV-1 replication steps are not effective in individuals chronically infected with HTLV-1. Once aggressive form ATL is developed in HTLV-1 carriers, their prognosis is poor even if they receive the intensive combined chemotherapy. Based on the characteristics of ATL cells, new drugs targeting ATL-specific cell surface markers and several signaling pathways, such as NF-kappaB have been developed. In addition, clinical observations show that ATL cells are highly immunogenic. Thus, establishment of the novel immune therapy is desired. In this review, we summarize recent progress in clinical and basic researches on new molecular-targeted therapies against this aggressive disease. PMID:25016813

Yasunaga, Jun-ichirou; Matsuoka, Masao

2014-06-01

179

Acid alpha-naphthyl acetate esterase in hairy cell leukemia cells and other cells of the hematopoietic system  

Microsoft Academic Search

Zusammenfassung Das Vorkommen und das Reaktionsbild vona-Naphthyl-Acetat-Esterase bei pH 5,8 (saure Esterase) wurde in den Zellen von 10 Haarzell-Leukämien untersucht. Alle 10 Haarzell-Leukämie-Fälle — darunter zwei Fälle mit nur vereinzelten tartratresistenten saure Phosphatase-positiven Zellen — waren mäßig stark bis stark saure Esterase-positiv. Die saure Esterase-Aktivität war in feinen bis groben Granula meist semizirkulär um den Zellkern verteilt. Dieses Reaktionsbild fand

G. Tolksdorf; H. Stein

1979-01-01

180

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. ...

181

Mixed lineage leukemia protein in normal and leukemic stem cells.  

PubMed

Transcription factors critical for normal hematopoietic stem cell functions are frequently mutated in acute leukemia leading to an aberrant re-programming of normal hematopoietic progenitor/stem cells into leukemic stem cells. Among them, re-arrangements of the mixed lineage leukemia gene (MLL), including chimeric fusion, partial tandem duplication (PTD), amplification and internal exonic deletion, represent one of the most common recurring oncogenic events and associate with very poor prognosis in human leukemias. Extensive research on wild type MLL and MLL-fusions has significant advanced our knowledge about their functions in normal and malignant hematopoiesis, which also provides a framework for the underlying pathogenic role of MLL re-arrangements in human leukemias. In contrast, research progress on MLL-PTD, MLL amplification and internal exonic deletion remains stagnant, in particular for the last two abnormalities where mouse model is not yet available. In this article, we will review the key features of both wild-type and re-arranged MLL proteins with particular focuses on MLL-PTD and MLL amplification for their roles in normal and malignant hematopoiesis. PMID:23598978

Yip, Bon Ham; So, Chi Wai Eric

2013-03-01

182

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.

183

The bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) blocks hairy cell leukaemia survival, proliferation and B cell receptor signalling: a new therapeutic approach.  

PubMed

B cell receptor (BCR) signalling plays a critical role in the progression of several B-cell malignancies, but its role in hairy cell leukaemia (HCL) is ambiguous. Bruton tyrosine kinase (BTK), a key player in BCR signalling, as well as B cell migration and adhesion, can be targeted with ibrutinib, a selective, irreversible BTK inhibitor. We analysed BTK expression and function in HCL and analysed the effects of ibrutinib on HCL cells. We demonstrated uniform BTK protein expression in HCL cells. Ibrutinib significantly inhibited HCL proliferation and cell cycle progression. Accordingly, ibrutinib also reduced HCL cell survival after BCR triggering with anti-immunoglobulins and abrogated the activation of kinases downstream of the BCR (PI3K and MAPK). Ibrutinib also inhibited BCR-dependent secretion of the chemokines CCL3 and CCL4 by HCL cells. Interestingly, ibrutinib inhibited also CXCL12-induced signalling, a key pathway for bone marrow homing. Collectively, our data support the clinical development of ibrutinib in patients with HCL. PMID:24697238

Sivina, Mariela; Kreitman, Robert J; Arons, Evgeny; Ravandi, Farhad; Burger, Jan A

2014-07-01

184

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.

185

Class II human leucocyte antigen DRB1*11 in hairy cell leukaemia patients with and without haemolytic uraemic syndrome.  

PubMed

Frequencies of human leucocyte antigens (HLA) were determined in 287 classic hairy cell leukaemia (HCL) patients. With respect to both population (n = 287) and allele (2n = 574) frequency respectively, the most common HLA class I and II antigens expressed were HLA-A*02 (49·1% and 28·6%), HLA-B*07 (21·3% and 11·1%), HLA-C*07 (46·7 and 28·2%), HLA-DQB1*03 (62·7% and 37·3%), HLA-DRB1*11 (30·0% and 16·0%) and HLA-DRB4*01 (45·3% and 29·6%). In comparing 6-14 databases of control Caucasians to 267 Caucasian HCL patients, only HLA-DRB1*11 was consistently over-represented in HCL, 31·1% of patients vs. 17-19·9% of controls (P = 0·0055 to <0·0001) and 16·5% of alleles vs. 6·5-12·3% of control alleles (P = 0·022 to <0·0001). HLA-DRB1*11 is a known risk factor for acquired thrombotic microangiopathy. Anti-CD22 recombinant immunotoxin BL22 in HCL was associated with a 12% incidence of completely reversible grade 3-4 haemolytic uraemic syndrome (HUS), mainly during the second or third retreatment cycle. Of 49 HCL patients receiving ?2 cycles of BL22, 7 (14%) had HUS and HLA-DRB1*11 was expressed in 71% of 7 with HUS compared with only 21% of 42 without (P = 0·015). These data suggest that DBR1*11 may be a marker for increased susceptibility to HCL and, among HCL patients, could be a risk factor for BL22-induced HUS. PMID:24931452

Arons, Evgeny; Adams, Sharon; Venzon, David J; Pastan, Ira; Kreitman, Robert J

2014-09-01

186

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

187

Donor cell leukemia: insight into cancer stem cells and the stem cell niche  

Microsoft Academic Search

Donor cell leukemia (DCL) is a rare compli- cation of hematopoietic cell transplanta- tion (HCT). Its incidence has been re- ported between 0.12% and 5%, although the majority of cases are anecdotal. The mechanisms of leukemogenesis in DCL may be distinct from other types of leuke- mia. Possible causes of DCL include on- cogenic alteration or premature aging of transplanted

Catherine M. Flynn; Dan S. Kaufman

2007-01-01

188

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.

189

Aplastic anemia and pure red cell aplasia associated with large granular lymphocyte leukemia  

Microsoft Academic Search

Aplastic anemia (AA) and pure red cell aplasia (PRCA) are two of the various types of immune-mediated cytopenias that can be associated with large granular lymphocyte (LGL) leukemia. We review the experience on LGL leukemia-associated AA and PRCA in the published literature. In the setting of LGL leukemia, AA is found rarely, while PRCA is frequent. However, the diagnosis of

Ronald S Go; John A Lust; Robert L Phyliky

2003-01-01

190

BCL6-mediated repression of p53 is critical for leukemia stem cell survival in chronic myeloid leukemia  

PubMed Central

Chronic myeloid leukemia (CML) is induced by the oncogenic BCR-ABL1 tyrosine kinase and can be effectively treated for many years with tyrosine kinase inhibitors (TKIs). However, unless CML patients receive life-long TKI treatment, leukemia will eventually recur; this is attributed to the failure of TKI treatment to eradicate leukemia-initiating cells (LICs). Recent work demonstrated that FoxO factors are critical for maintenance of CML-initiating cells; however, the mechanism of FoxO-dependent leukemia initiation remained elusive. Here, we identified the BCL6 protooncogene as a critical effector downstream of FoxO in self-renewal signaling of CML-initiating cells. BCL6 represses Arf and p53 in CML cells and is required for colony formation and initiation of leukemia. Importantly, peptide inhibition of BCL6 in human CML cells compromises colony formation and leukemia initiation in transplant recipients and selectively eradicates CD34+ CD38? LICs in patient-derived CML samples. These findings suggest that pharmacological inhibition of BCL6 may represent a novel strategy to eradicate LICs in CML. Clinical validation of this concept could limit the duration of TKI treatment in CML patients, which is currently life-long, and substantially decrease the risk of blast crisis transformation. PMID:21911423

Hurtz, Christian; Hatzi, Katerina; Cerchietti, Leandro; Braig, Melanie; Park, Eugene; Kim, Yong-mi; Herzog, Sebastian; Ramezani-Rad, Parham; Jumaa, Hassan; Muller, Martin C.; Hofmann, Wolf-Karsten; Hochhaus, Andreas; Ye, B. Hilda; Agarwal, Anupriya; Druker, Brian J.; Shah, Neil P.; Melnick, Ari M.

2011-01-01

191

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

192

Chronic lymphocytic leukemia: a disease of activated monoclonal B cells  

PubMed Central

B-cell type chronic lymphocytic leukemia (CLL) has long been considered a disease of resting lymphocytes. However cell surface and intracellular phenotypes suggest that most CLL cells are activated cells, although only a small subset progresses beyond the G1 stage of the cell cycle. In addition, traditional teaching says that CLL cells divide rarely, and therefore the buildup of leukemic cells is due to an inherent defect in cell death. However, in vivo labeling of CLL cells indicates a much more active rate of cell birth than originally estimated, suggesting that CLL is a dynamic disease. Here we review the observations that have led to these altered views of the activation state and proliferative capacities of CLL cells and also provide our interpretation of these observations in light of their potential impact on patients. PMID:20620969

Damle, Rajendra N.; Calissano, Carlo; Chiorazzi, Nicholas

2010-01-01

193

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

2014-10-09

194

[Expression of B7-H1 gene in leukemia cells and its clinical significance].  

PubMed

This study was purposed to investigate the expression of B7-H1 gene in leukemia cells and its clinical significance. The expression of B7-H1 mRNA was detected by SYBR Green I real-time quantitative PCR in a panel of 9 leukemia cell lines, 4 leukemia cell lines induced with IFN-?, the bone marrow mononuclear cells (BMMNC) from 59 initial leukemia patients and 10 dendritic cells (DC) derived from BMMNC of initial leukemia patients, 2 solid tumour cell lines and BMMNC from 10 normal persons. The correlation between the clinical features of 59 acute leukemia patients and the expression level of B7-H1 mRNA in leukemia cells was analyzed. The results showed that the lower level of B7-H1 mRNA expression was found in leukemia cell lines and primary acute leukemia cells, but the expression level of B7-H1 mRNA was up-regulated significantly in the leukemia cell lines induced by IFN-? and DC derived from BMMNC of leukemia patients. The expression level of B7-H1 mRNA in non complete remission (CR) patients after therapy was significantly higher than that in CR patients. It is concluded that the expression level of B7-H1 mRNA in leukemia cells is lower, but is up-regulated when affected by some factors. A correlation exists between the expression level of B7-H1 gene in leukemia cells and response of patients to therapy. PMID:22739151

Li, Xin; Sun, Wan-Jun; Xu, Yan; Li, Zeng-Jun; Yu, Zhen; Deng, Shu-Hui; Li, Chang-Hong; Qiu, Lu-Gui

2012-06-01

195

Reprogramming of MLL-AF9 leukemia cells into pluripotent stem cells  

PubMed Central

The ‘Yamanaka factors' (Oct4, Sox2, Klf4 and c-Myc) are able to generate induced pluripotent stem (iPS) cells from different cell types. However, to what degree primary malignant cells can be reprogrammed into a pluripotent state has not been vigorously assessed. We established an acute myeloid leukemia (AML) model by overexpressing the human mixed-lineage leukemia-AF9 (MLL-AF9) fusion gene in mouse hematopoietic cells that carry Yamanaka factors under the control of doxycycline (Dox). On addition of Dox to the culture, the transplantable leukemia cells were efficiently converted into iPS cells that could form teratomas and produce chimeras. Interestingly, most chimeric mice spontaneously developed the same type of AML. Moreover, both iPS reprogramming and leukemia reinitiation paths could descend from the same leukemia-initiating cell. RNA-seq analysis showed reversible global gene expression patterns between these interchangeable leukemia and iPS cells on activation or reactivation of MLL-AF9, suggesting a sufficient epigenetic force in driving the leukemogenic process. This study represents an important step for further defining the potential interplay between oncogenic molecules and reprogramming factors during MLL leukemogenesis. More importantly, our reprogramming approach may be expanded to characterize a range of hematopoietic malignancies in order to develop new strategies for clinical diagnosis and treatment. PMID:24150221

Liu, Y; Cheng, H; Gao, S; Lu, X; He, F; Hu, L; Hou, D; Zou, Z; Li, Y; Zhang, H; Xu, J; Kang, L; Wang, Q; Yuan, W; Gao, S; Cheng, T

2014-01-01

196

Expression profile of CREB knockdown in myeloid leukemia cells  

PubMed Central

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 affect long-term hematopoietic reconstitution. Methods To understand downstream pathways regulating CREB, we performed expression profiling with RNA from the K562 myeloid leukemia cell line transduced with CREB shRNA. Results By combining our expression data from CREB knockdown cells with prior ChIP data on CREB binding we were able to identify a list of putative CREB regulated genes. We performed extensive analyses on the top genes in this list as high confidence CREB targets. We found that this list is enriched for genes involved in cancer, and unexpectedly, highly enriched for histone genes. Furthermore, histone genes regulated by CREB were more likely to be specifically expressed in hematopoietic lineages. Decreased expression of specific histone genes was validated in K562, TF-1, and primary AML cells transduced with CREB shRNA. Conclusion We have identified a high confidence list of CREB targets in K562 cells. These genes allow us to begin to understand the mechanisms by which CREB contributes to acute leukemia. We speculate that regulation of histone genes may play an important role by possibly altering the regulation of DNA replication during the cell cycle. PMID:18801183

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

2008-01-01

197

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. ...

198

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

2014-05-28

199

FLT3 mutations in acute myeloid leukemia cell lines  

Microsoft Academic Search

Internal tandem duplications (ITD) and D835 point mutations of the receptor tyrosine kinase (RTK) FLT3 are found in a high proportion of cases with acute myeloid leukemia (AML). These genetic aberrations may lead to the constitutive activation of the receptor, thus providing the molecular basis for a persisting growth stimulus. We have screened 69 AML-derived cell lines for FLT3 mutations.

H Quentmeier; J Reinhardt; M Zaborski; H G Drexler

2003-01-01

200

Acute leukemia after successful chemotherapy for oat cell carcinoma  

SciTech Connect

A report of acute myelomonocytic leukemia following successful therapy for oat cell carcinoma is presented. The patient had been treated with extensive cytotoxic and radiation therapy, and was without clinical evidence of disease at one year follow-up. Eighteen months later, a peripheral smear revealed numerous blasts with monocytoid characteristics. This unusual presentation is discussed and compared with several other cases appearing in the recent literature.

Rose, V.L.; Keppen, M.D.; Eichner, E.R.; Pitha, J.V.; Murray, J.L.

1983-01-01

201

Transcriptional regulatory networks downstream of TAL1/SCL in T-cell acute lymphoblastic leukemia  

E-print Network

expression leads to T-cell acute lymphoblastic leukemia (T-ALL). TAL1 is expressed by the leukemic cellsNEOPLASIA Transcriptional regulatory networks downstream of TAL1/SCL in T-cell acute lymphoblastic pathogene- sis of human T-cell acute lymphoblastic leukemia (T-ALL); however, oncogenic transcriptional

Liu, Xiaole Shirley

202

Fludarabine Phosphate, Low-Dose Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney 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); B-cell Chronic Lymphocytic Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Childhood Renal Cell Carcinoma; Chronic Phase Chronic Myelogenous Leukemia; Clear Cell Renal Cell Carcinoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular 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; Splenic Marginal Zone Lymphoma; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer; T-cell Large Granular Lymphocyte Leukemia; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Waldenström Macroglobulinemia

2014-10-16

203

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

ClinicalTrials.gov

Contiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Childhood 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; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

2014-09-30

204

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

205

Dendritic Cells Pulsed with Leukemia Cell-Derived Exosomes More Efficiently Induce Antileukemic Immunities  

PubMed Central

Dendritic cells (DCs) and tumor cell-derived exosomes have been used to develop antitumor vaccines. However, the biological properties and antileukemic effects of leukemia cell-derived exosomes (LEXs) are not well described. In this study, the biological properties and induction of antileukemic immunity of LEXs were investigated using transmission electron microscopy, western blot analysis, cytotoxicity assays, and animal studies. Similar to other tumor cells, leukemia cells release exosomes. Exosomes derived from K562 leukemia cells (LEXK562) are membrane-bound vesicles with diameters of approximately 50–100 ?m and harbor adhesion molecules (e.g., intercellular adhesion molecule-1) and immunologically associated molecules (e.g., heat shock protein 70). In cytotoxicity assays and animal studies, LEXs-pulsed DCs induced an antileukemic cytotoxic T-lymphocyte immune response and antileukemic immunity more effectively than did LEXs and non-pulsed DCs (P<0.05). Therefore, LEXs may harbor antigens and immunological molecules associated with leukemia cells. As such, LEX-based vaccines may be a promising strategy for prolonging disease-free survival in patients with leukemia after chemotherapy or hematopoietic stem cell transplantation. PMID:24622345

Wei, Wei; Shen, Chang; Deng, Xiaohui; Chen, Linjun; Ma, Liyuan; Hao, Siguo

2014-01-01

206

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

207

Dynamics of Leukemia Stem-like Cell Extinction in Acute Promyelocytic Leukemia.  

PubMed

Many tumors are believed to be maintained by a small number of cancer stem-like cells, where cure is thought to require eradication of this cell population. In this study, we investigated the dynamics of acute promyelocytic leukemia (APL) before and during therapy with regard to disease initiation, progression, and therapeutic response. This investigation used a mathematical model of hematopoiesis and a dataset derived from the North American Intergroup Study INT0129. The known phenotypic constraints of APL could be explained by a combination of differentiation blockade of PML-RAR?-positive cells and suppression of normal hematopoiesis. All-trans retinoic acid (ATRA) neutralizes the differentiation block and decreases the proliferation rate of leukemic stem cells in vivo. Prolonged ATRA treatment after chemotherapy can cure patients with APL by eliminating the stem-like cell population over the course of approximately one year. To our knowledge, this study offers the first estimate of the average duration of therapy that is required to eliminate stem-like cancer cells from a human tumor, with the potential for the refinement of treatment strategies to better manage human malignancy. Cancer Res; 74(19); 5386-96. ©2014 AACR. PMID:25082816

Werner, Benjamin; Gallagher, Robert E; Paietta, Elisabeth M; Litzow, Mark R; Tallman, Martin S; Wiernik, Peter H; Slack, James L; Willman, Cheryl L; Sun, Zhuoxin; Traulsen, Arne; Dingli, David

2014-10-01

208

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

209

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

210

Telomerase Regulation and Telomere Maintenance during Human T-cell Leukemia/Lymphoma Virus (HTLV-I) Transformation  

E-print Network

Human T-cell leukemia/lymphoma virus (HTLV-I) is the etiological agent of the lymphoproliferative disorder, adult T-cell leukemia/lymphoma (ATLL) and the neurodegenerative disease, tropical spastic paraparesis/HTLV-I-associated ...

Bellon, Marcia Lynn

2008-04-29

211

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

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; 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 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

2014-10-02

212

NCI Scientists Discover How T-Cell Leukemia Viruses Evade Body's Defense Mechanisms  

Cancer.gov

NCI scientists have discovered how human T-cell leukemia virus type 1 (HTLV-1), which infects about 20 million people worldwide, evades being held in check by one of the body's natural defense mechanisms. An active infection with HTLV-1 leads to T-cell leukemia in up to five percent of all cases worldwide.

213

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

214

Molecular signatures of chronic myeloid leukemia stem cells  

PubMed Central

BCR-ABL tyrosine kinase inhibitors (TKIs) are effective in controlling Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) are unlikely to cure the disease because TKIs are unable to eradicate leukemia stem cells (LSCs) responsible for the disease relapse even after tyrosine kinase inhibition. In addition, the TKI resistance of LSCs is not associated with the BCR-ABL kinase domain mutations. These observations indicate that TKI-insensitive LSCs and TKI-sensitive leukemic progenitor cells are biologically different, which leads us to believe that LSCs and more differentiated leukemic cells have different genetic mechanisms. Further study of LSCs to identify the novel gene signatures and mechanisms that control the function and molecular phenotype of LSCs is critical. In this mini-review, we will discuss our current understanding of the biology of LSCs and novel genes that could serve as a molecular signature of LSCs in CML. These novel genes could also serve as potential targets for eradicating LSCs in CML. PMID:24252550

2013-01-01

215

Human T-cell leukemia virus type I (HTLV-I) infection and the onset of adult T-cell leukemia (ATL)  

Microsoft Academic Search

The clinical entity of adult T-cell leukemia (ATL) was established around 1977, and human T-cell leukemia virus type 1 (HTLV-I) was subsequently identified in 1980. In the 25 years since the discovery of HTLV-I, HTLV-I infection and its associated diseases have been extensively studied, and many of their aspects have been clarified. However, the detailed mechanism of leukemogenesis remains unsolved

Masao Matsuoka

2005-01-01

216

Isolation and Transmission of Human Retrovirus (Human T-Cell Leukemia Virus)  

Microsoft Academic Search

Nine new isolates of human T-cell leukemia-lymphoma virus (HTLV) were obtained from cells of seven patients with malignancies of mature T cells and from two clinically normal relatives of a T-cell leukemia patient. These people were from the United States, Israel, the West Indies, and Japan. The virus was detected in the fresh T cells and was isolated from the

M. Popovic; P. S. Sarin; M. Robert-Gurroff; V. S. Kalyanaraman; D. Mann; J. Minowada; R. C. Gallo

1983-01-01

217

Donor cell leukemia after allogeneic peripheral blood stem cell transplantation: a case report and literature review  

Microsoft Academic Search

A 49-year-old male developed recurrent acute myeloid leukemia 27 months after allogeneic peripheral blood stem cell transplantation\\u000a (PBSCT) from an HLA-identical brother. The immunophenotype of the blastic cell population was incompatible with that of the\\u000a pre-transplant blast cells; a mutation in C\\/EBPA gene was found in the pre-transplant blast cells that was not present in the post-transplant blast cells, and short

Makoto Murata; Yuichi Ishikawa; Haruhiko Ohashi; Seitaro Terakura; Kazutaka Ozeki; Hitoshi Kiyoi; Tomoki Naoe

2008-01-01

218

Establishment of hairy root cultures of Ammi majus  

Microsoft Academic Search

Axenically grown Ammi majus plantlets were inoculated with seven different Agrobacterium rhizogenes strains. Hairy root lines were established only after inoculation with the two agropine strains: A4 and LBA9402. The growth rate of hairy root cultures was about thirty times faster than that of callus and cell suspension cultures. Polymerase chain reaction with primers for the genes rolB and rolC

Aleksandra Królicka; Izabela Staniszewska; Krzysztof Bielawski; Edmund Mali?ski; Janusz Szafranek; Ewa ?ojkowska

2001-01-01

219

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

E-print Network

Leukemia . Author manuscript Page /1 12 Follicular lymphoma cell niche: identification equally to this work Abstract Follicular lymphoma (FL) B cells contract tight connections, Tumor-Infiltrating ; physiology ; Lymphoma, Follicular ; etiology ; immunology ; Oligonucleotide Array

Boyer, Edmond

220

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

221

Extremal Hairy Black Holes  

E-print Network

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 at low temperature the Reissner-Nordstr\\"om black hole is thermodynamically preferred, while if the space is AdS the hairy charged black hole is thermodynamically preferred at low temperature.

Gonzalez, P A; Saavedra, Joel; Vasquez, Yerko

2014-01-01

222

Inhibition of constitutively active Jak-Stat pathway suppresses cell growth of human T-cell leukemia virus type 1-infected T-cell lines and primary adult T-cell leukemia cells  

Microsoft Academic Search

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1), the etiologic agent for adult T-cell leukemia (ATL), induces cytokine-independent proliferation of T-cells, associated with the acquisition of constitutive activation of Janus kinases (Jak) and signal transducers and activators of transcription (Stat) proteins. Our purposes in this study were to determine whether activation of Jak-Stat pathway is responsible for the proliferation and

Mariko Tomita; Hirochika Kawakami; Jun-nosuke Uchihara; Taeko Okudaira; Masato Masuda; Takehiro Matsuda; Yuetsu Tanaka; Kazuiku Ohshiro; Naoki Mori

2006-01-01

223

Cutaneous Langerhans cell histiocytosis in elderly with chronic myelomonocytic leukemia.  

PubMed

Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm characterized by clonal proliferation of Langerhans cells in multi-organ systems including skin, bone, pituitary gland, liver and spleen. Skin-limited involvement of LCH usually indicates an indolent clinical course; however, in rare cases, LCH is accompanied by other myeloproliferative disorders, which may determine the prognosis. An 82-year old Japanese man presented with numerous asymptomatic facial papules clinically simulating rhinophyma. Although findings of histopathology and general examination including bone marrow biopsy led to the diagnosis of cutaneous LCH, he died from chronic myelomonocytic leukemia, which emerged 10 months after the initial diagnosis of LCH. The previously reported cases of LCH concomitant with other hematological disorders are also summarized and described compared with the present case. PMID:24628074

Iwasaki, Takeshi; Takahashi, Ichiro; Nagashima, Takahiro; Igawa, Satomi; Komatsu, Shigetsuna; Honma, Masaru; Ishida-Yamamoto, Akemi; Iizuka, Hajime

2014-03-01

224

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

225

Association of Oxidative Stress with Realgar-Induced Differentiation in Human Leukemia HL60 Cells  

Microsoft Academic Search

Background: Realgar (arsenic sulfide, As4S4) has been shown to have clinical efficacy in patients with newly diagnosed and relapsed acute promyelocytic leukemia. Mechanistic studies have demonstrated that realgar is able to induce cell differentiation. Methods: The oxidative stress in the realgar-induced differentiation was examined with human leukemia HL-60 cells. Cell differentiation was evaluated by the expression of cell surface antigen

Li-Wen Wang; Yan-Ling Shi; Nan Wang; Bao-Di Gou; Tian-Lan Zhang; Kui Wang

2009-01-01

226

Lymphokine Production by Cultured Human T Cells Transformed by Human T-Cell Leukemia-Lymphoma Virus-I  

Microsoft Academic Search

Cell-free conditioned media from human T cells transformed by human T-cell leukemia-lymphoma virus (HTLV-I) were tested for the production of soluble biologically active factors, including several known lymphokines. The cell lines used were established from patients with T-cell leukemia-lymphoma and from human umbilical cord blood and bone marrow leukocytes transformed by HTLV-I in vitro. All of the cell lines liberated

S. Z. Salahuddin; P. D. Markham; S. G. Lindner; J. Gootenberg; M. Popovic; H. Hemmi; P. S. Sarin; R. C. Gallo

1984-01-01

227

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

228

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.

229

[Clinical features of adult T-cell leukemia].  

PubMed

Adult T-cell leukemia (ATL) is T-cell leukemic non Hodgkins' malignant lymphoma; 73 percent of 199 non Hodgkins' lymphomas were of T-cell origin, and 58 percent of these T-cell lymphomas were ATL in Nagasaki, Japan. ATL cells are mostly characteristic in the specific nuclear indentations. These cells have a commonly helper T-cell phenotype on the reaction to the Leu series monoclonal antibody, and the cells showed a suppressor function to normal B-cell differentiation by PWM. Miscellaneous infections, probably due to T-cell disfunction have been frequently experienced in ATL. Pulmonary infections, especially interstitial pneumonitis, were characteristic. Bone destraction through osteocrast proliferation was suggested to be the main cause of hypercalcemia. Many cases with familiar disposition have been found in ATL and T-ML, and 3 siblings having ATL and T-ML were presented. ATLA antibody was positive in all cases of ATL and 63 percent of T-ML. Positive rate of ATLA antibody in healthy spouses and siblings of ATL and T-ML patients was high. ATLA (antigen) on the mononuclear cells of almost all the ATL and ATLA antibody positive T-ML was positive. Peripheral blood mononuclear cells of 2 cases of mycosis fungoides were also positive for ATLA. Probably pre ATL cases with low grade leukocytosis and the presence of ATL cell like lymphocytes and positive rate of ATLA antibody and antigen of these cases were presented. By the chromosome study of 14 cases of ATL, chromosome aberrations of No. 2, 3 and 18 were frequently observed. PMID:6603819

Ichimaru, M

1983-02-01

230

Surface functions during mitosis in rat basophilic leukemia cells  

PubMed Central

At the entry into mitosis, cells abruptly lose membrane activities such as phagocytosis, pinocytosis, and capping. The present studies test if mitotic cells also resist functional responses to cell surface ligand- receptor interactions. The IgE receptors of RBL-2H3 rat basophilic leukemia cells were labeled with anti-dinitrophenol IgE (anti-DNP-IgE) and then cross-linked with multivalent ligands (DNP-bovine serum albumin [BSA]; DNP-B-phycoerythrin; DNP-BSA-gold). IgE-receptor cross- linking modulates cell surface organization and function and releases serotonin and other mediators of allergic and asthmatic reactions from interphase cells (Pfeiffer, J. R., JC. Seagrave, B. H. Davis, G. G. Deanin, and J. M. Oliver, 1985, J. Cell Biol., 101:2145-2155). It was found that anti-DNP-IgE-receptor complexes are preserved on the cell surface throughout mitosis; they continue to bind DNP-proteins, and the resulting antigen-IgE-receptor complexes can redistribute to coated pits on the cell surface. Furthermore, there is no loss of [3H]serotonin through mitosis. Nevertheless, antigen-stimulated [3H]- serotonin release is strongly impaired in mitotic-enriched as compared with mixed interphase or G1-enriched cell populations. In addition, antigen binding transforms the surface of interphase cells from a microvillous to a plicated topography and stimulates the uptake of fluorescein isothiocyanate-conjugated dextran by fluid pinocytosis. Mitotic cells maintain a microvillous surface topography after antigen treatment, and fluid pinocytosis virtually ceases from prometaphase to telophase. Phorbol myristate acetate, a tumor promoter that activates protein kinase C, restores surface ruffling activity to mitotic cells. Thus, the mitosis-specific freezing of membrane and secretory responses is most likely due to the failure of transmembrane signaling. PMID:2933415

1985-01-01

231

Regulation of myeloid leukemia by the cell fate determinant Musashi  

PubMed Central

Chronic myelogenous leukemia (CML) can progress from an indolent chronic phase to an aggressive blast crisis phase1 but the molecular basis of this transition remains poorly understood. Here we have used mouse models of CML2,3 to show that disease progression is regulated by the Musashi-Numb signaling axis4,5. Specifically, we find that chronic phase is marked by high and blast crisis phase by low levels of Numb expression, and that ectopic expression of Numb promotes differentiation and impairs advanced phase disease in vivo. As a possible explanation for the decreased levels of Numb in blast crisis, we show that NUP98-HOXA9, an oncogene associated with blast crisis CML6,7, can trigger expression of the RNA binding protein Musashi2 (Msi2) which in turn represses Numb. Importantly, loss of Msi2 restores Numb expression and significantly impairs the development and propagation of blast crisis CML in vitro and in vivo. Finally, we show that Msi2 expression is not only highly upregulated during human CML progression but is also an early indicator of poorer prognosis. These data show that the Musashi-Numb pathway can control the differentiation of CML cells, and raise the possibility that targeting this pathway may provide a new strategy for therapy of aggressive leukemias. PMID:20639863

Ito, Takahiro; Kwon, Hyog Young; Zimdahl, Bryan; Congdon, Kendra L.; Blum, Jordan; Lento, William E.; Zhao, Chen; Lagoo, Anand; Gerrard, Gareth; Foroni, Letizia; Goldman, John; Goh, Harriet; Kim, Soo-Hyun; Kim, Dong-Wook; Chuah, Charles; Oehler, Vivian G.; Radich, Jerald P.; Jordan, Craig T.; Reya, Tannishtha

2010-01-01

232

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

SciTech Connect

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. At time of diagnosis, patient ages ranged from 21 to 60 years (mean, 41.8 years) and the interval from time of nuclear test to diagnosis from two to 19 years (mean, 14.2 years). Film-badge records, which are available for eight of the nine men, indicated gamma radiation exposure levels ranging from 0 to 2977 mrem (mean, 1033 mrem). Mean film-badge gamma dose for the entire Smoky cohort was 466.2 mrem.

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

1980-10-03

233

S100A8 Contributes to Drug Resistance by Promoting Autophagy in Leukemia Cells  

PubMed Central

Autophagy is a double-edged sword in tumorigenesis and plays an important role in the resistance of cancer cells to chemotherapy. S100A8 is a member of the S100 calcium-binding protein family and plays an important role in the drug resistance of leukemia cells, with the mechanisms largely unknown. Here we report that S100A8 contributes to drug resistance in leukemia by promoting autophagy. S100A8 level was elevated in drug resistance leukemia cell lines relative to the nondrug resistant cell lines. Adriamycin and vincristine increased S100A8 in human leukemia cells, accompanied with upregulation of autophagy. RNA interference-mediated knockdown of S100A8 restored the chemosensitivity of leukemia cells, while overexpression of S100A8 enhanced drug resistance and increased autophagy. S100A8 physically interacted with the autophagy regulator BECN1 and was required for the formation of the BECN1-PI3KC3 complex. In addition, interaction between S100A8 and BECN1 relied upon the autophagic complex ULK1-mAtg13. Furthermore, we discovered that exogenous S100A8 induced autophagy, and RAGE was involved in exogenous S100A8-regulated autophagy. Our data demonstrated that S100A8 is involved in the development of chemoresistance in leukemia cells by regulating autophagy, and suggest that S100A8 may be a novel target for improving leukemia therapy. PMID:24820971

Yang, Minghua; Zeng, Pei; Kang, Rui; Yu, Yan; Yang, Liangchun; Tang, Daolin; Cao, Lizhi

2014-01-01

234

Cell Cycle-Specific Function of Ikaros in Human Leukemia  

PubMed Central

Background The loss of Ikaros is associated with the development of B and T cell leukemia. Data on Ikaros function, including its role as a tumor suppressor and a regulator of cell cycle progression, come almost exclusively from murine studies; little is known of the mechanisms that regulate human Ikaros function. Our studies are the first to examine the function and regulation of human Ikaros isoforms during the cell cycle in human ALL. Procedures Electromobility shift assay (EMSA), confocal microscopy, and phosphopeptide mapping were used to study Ikaros function during different stages of the cell cycle. Results The DNA-binding activity of human Ikaros complexes undergoes dynamic changes as the cell cycle progresses. In S phase, Ikaros DNA-binding affinity for regulatory regions of its target genes decreases, while its binding to pericentromeric heterochromatin is preserved and correlates with Ikaros pericentromeric localization. These S phase-specific changes in Ikaros function are controlled by phosphorylation via the CK2 kinase pathway. During cell cycle progression, the subcellular pericentromeric localization of the largest human Ikaros isoforms is different from that in mouse cells, suggesting unique functions for human Ikaros. Conclusions Our results demonstrate that the function of Ikaros is cell cycle-specific and controlled by CK2-mediated phosphorylation during S phase of the cell cycle in human T-cell and B-cell ALL. The differences we observe in murine and human Ikaros function highlight the importance of using human cells in studies of ALL. These data identify the CK2 pathway as a target for therapies in ALL. PMID:22106042

Li, Zhanjun; Song, Chunhua; Ouyang, Hongsheng; Lai, Liangxue; Payne, Kimberly J.; Dovat, Sinisa

2011-01-01

235

What Is Chronic Myeloid Leukemia?  

MedlinePLUS

... about chronic myeloid leukemia? What is chronic myeloid leukemia? Chronic myeloid leukemia (CML), also known as chronic ... and start making antibodies to fight them. How leukemia starts Any blood-forming or lymphoid cells can ...

236

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 ...

237

Malignant hematopoietic cell lines: in vitro models for the study of natural killer cell leukemia–lymphoma  

Microsoft Academic Search

Malignancies involving natural killer (NK) cells are rare disorders. The complexity of NK cell-involving disorders has only recently been appreciated. Modern classifications discern immature (precursor) from mature NK cell leukemias–lymphomas. Continuous NK leukemia–lymphoma cell lines represent important model systems to study these neoplasms. While there are a number of putative NK cell lines which are, however, either not characterized, not

HG Drexler; Y Matsuo

2000-01-01

238

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

239

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

2013-12-30

240

MIP-1?/CCL3-mediated maintenance of leukemia-initiating cells in the initiation process of chronic myeloid leukemia.  

PubMed

In the initiation process of chronic myeloid leukemia (CML), a small number of transformed leukemia-initiating cells (LICs) coexist with a large number of normal hematopoietic cells, gradually increasing thereafter and eventually predominating in the hematopoietic space. However, the interaction between LICs and normal hematopoietic cells at the early phase has not been clearly delineated because of the lack of a suitable experimental model. In this study, we succeeded in causing a marked leukocytosis resembling CML from restricted foci of LICs in the normal hematopoietic system by direct transplantation of BCR-ABL gene-transduced LICs into the bone marrow (BM) cavity of nonirradiated mice. Herein, we observed that BCR-ABL(+)lineage(-)c-kit(-) immature leukemia cells produced high levels of an inflammatory chemokine, MIP-1?/CCL3, which promoted the development of CML. Conversely, ablation of the CCL3 gene in LICs dramatically inhibited the development of CML and concomitantly reduced recurrence after the cessation of a short-term tyrosine kinase inhibitor treatment. Finally, normal hematopoietic stem/progenitor cells can directly impede the maintenance of LICs in BM in the absence of CCL3 signal. PMID:24166712

Baba, Tomohisa; Naka, Kazuhito; Morishita, Soji; Komatsu, Norio; Hirao, Atsushi; Mukaida, Naofumi

2013-11-18

241

Concurrent chronic lymphocytic leukemia and merkel cell carcinoma in primary skin tumor and metastatic lymph node.  

PubMed

Association between chronic lymphocytic leukemia and other malignancies has been known for a long time. This epidemiological phenomenon is explained by immunosuppression caused by disease itself or by the applied therapy. Merkel cell carcinoma is a rare malignant tumor of the skin of neuroendocrine origin diagnosed almost exclusively in immunocompromised host. We presented an unique case of coexisting infiltration of chronic lymphocytic leukemia cells within primary cutaneous Merkel cell carcinoma and metastatic lymph node in young HIV-negative female patient. PMID:25332636

Popovic, Lazar; Jovanovic, Darjana; Petrovic, Dragana; Nikin, Zoran; Matovina-Brko, Gorana; Trifunovic, Jasna; Kolarov-Bjelobrk, Ivana

2014-09-01

242

Interferon-? Therapy following Autologous Peripheral Blood Stem Cell Transplantation for Adult T Cell Leukemia\\/Lymphoma  

Microsoft Academic Search

In the present report, we describe a case of adult T cell leukemia\\/lymphoma (ATLL), a 58-year-old woman, successfully treated with interferon (IFN)-? following autologous peripheral blood stem cell transplantation (auto-PBSCT). The patient remains in remission with full performance status for more than 12 months. Auto-PBSCT reduced the abdominal lymphoma mass and IFN-? eliminated residual tumor cells, possibly through the induction

Hiroshi Fujiwara; Naomichi Arima; Yuichi Akasaki; Hideo Ohtsubo; Atsuo Ozaki; Toshimasa Kukita; Kakushi Matsushita; Kosei Arimura; Yukio Suruga; Shinichi Wakamatsu; Tadashi Matsumoto; Shiroh Hidaka; Yoshito Eizuru; Chuwa Tei

2002-01-01

243

Improved outcome of adult T cell leukemia\\/lymphoma with allogeneic hematopoietic stem cell transplantation  

Microsoft Academic Search

Adult T cell leukemia\\/lymphoma (ATL) is a poor prognosis T cell malignancy. In order to improve the outcome, we employed allogeneic stem cell transplantation (allo-SCT) for ATL in 10 patients, nine of whom were from HLA-identical siblings and one from an unrelated donor. Conditioning regimens varied among the patients except that all received total body irradiation. The patients tolerated the

A Utsunomiya; Y Miyazaki; Y Takatsuka; S Hanada; K Uozumi; S Yashiki; M Tara; F Kawano; Y Saburi; H Kikuchi; M Hara; H Sao; Y Morishima; Y Kodera; S Sonoda; M Tomonaga

2001-01-01

244

Mast cell leukemia with prolonged survival on PKC412/midostaurin  

PubMed Central

Mast cell leukemia (MCL) is a rare and aggressive form of systemic mastocytosis. There are approximately 50 reported cases since 1950s. MCL is refractory to cytoreduction chemotherapy and the average survival is only six months. We report a MCL case in a 71 year-old woman with high tumor load at the initial presentation in 2005, who did not respond to either interleukin-2 or dasatinib therapy. After enrolled in a clinical trial of PKC412 (or Midostaurin) with a daily dose of 100 mg, the patient responded well to PKC412 and became transfusion independent in three months. Since then, her disease had been stably controlled. This is the first report of a high-tumor-load MCL case which achieved prolonged survival (101 months) by PKC 412. The 101-month overall survival is the longest among reported MCL cases in the English literature. PMID:25031773

Xu, Xiangdong; Kreisel, Friederike H; Frater, John L; Hassan, Anjum

2014-01-01

245

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

246

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

247

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

248

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

249

Targeting Aberrant Glutathione Metabolism to Eradicate Human Acute Myelogenous Leukemia Cells*  

PubMed Central

The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34+) leukemic versus normal specimens. Our data indicate that CD34+ AML cells have elevated expression of multiple glutathione pathway regulatory proteins, presumably as a mechanism to compensate for increased oxidative stress in leukemic cells. Consistent with this observation, CD34+ AML cells have lower levels of reduced glutathione and increased levels of oxidized glutathione compared with normal CD34+ cells. These findings led us to hypothesize that AML cells will be hypersensitive to inhibition of glutathione metabolism. To test this premise, we identified compounds such as parthenolide (PTL) or piperlongumine that induce almost complete glutathione depletion and severe cell death in CD34+ AML cells. Importantly, these compounds only induce limited and transient glutathione depletion as well as significantly less toxicity in normal CD34+ cells. We further determined that PTL perturbs glutathione homeostasis by a multifactorial mechanism, which includes inhibiting key glutathione metabolic enzymes (GCLC and GPX1), as well as direct depletion of glutathione. These findings demonstrate that primitive leukemia cells are uniquely sensitive to agents that target aberrant glutathione metabolism, an intrinsic property of primary human AML cells. PMID:24089526

Pei, Shanshan; Minhajuddin, Mohammad; Callahan, Kevin P.; Balys, Marlene; Ashton, John M.; Neering, Sarah J.; Lagadinou, Eleni D.; Corbett, Cheryl; Ye, Haobin; Liesveld, Jane L.; O'Dwyer, Kristen M.; Li, Zheng; Shi, Lei; Greninger, Patricia; Settleman, Jeffrey; Benes, Cyril; Hagen, Fred K.; Munger, Joshua; Crooks, Peter A.; Becker, Michael W.; Jordan, Craig T.

2013-01-01

250

Activation of Rac1 GTPase promotes leukemia cell chemotherapy resistance, quiescence and niche interaction.  

PubMed

Leukemia stem cells (LSCs) reside in bone marrow niche and receive important signals from the microenvironment that support self-renewal, maintain quiescence and endow LSC with the ability of chemotherapy resistance. Rac1 belongs to the small GTP-binding protein superfamily and is implicated in the interactions of hematopoietic progenitors and bone marrow niche. Our previous studies have shown that Rac1 is over-expressed in leukemia patients and activation of Rac1 GTPase is closely associated with the efficient migration of leukemia cells. However, the potential functions for Rac1 GTPase in LSCs behaviors and in the residence of leukemia cells in niche remain unknown. In this study, by forced expression of a dominant-negative form of Rac1 GTPase in a CD34(+) myeloid leukemia cell line, as well as bone marrow cells from leukemia patients, we show that inactivation of Rac1 GTPase causes impaired migration and enhances chemotherapeutic sensitivity. Inactivation of Rac1 in leukemia cells also lead to a reduction in the frequency of cells in quiescent state and inhibition of homing to bone marrow niche. Gene expression analysis shows that inactivation of Rac1 down-regulates the expression of several cell intrinsic cell cycle inhibitors such as p21, p27, and p57, as well as the extrinsic molecules that mediated the interaction of LSC with osteoblastic niche. Furthermore, we show that Rac1 mediated the localization in niche is further attributed to the maintenance of quiescence. Our results provide evidence for the critical role of Rac1 GTPase in leukemia cell chemotherapy resistance, quiescence maintenance and the interaction with bone marrow microenvironment. PMID:23726395

Wang, Ji-Ying; Yu, Pei; Chen, Shuying; Xing, Haiyan; Chen, Yirui; Wang, Min; Tang, Kejing; Tian, Zheng; Rao, Qing; Wang, Jianxiang

2013-10-01

251

BCL6 enables Ph+ acute lymphoblastic leukemia cells to survive BCR-ABL1 kinase inhibition  

PubMed Central

Tyrosine kinase inhibitors (TKI) are widely used to treat patients with leukemia driven by BCR-ABL11 and other oncogenic tyrosine kinases2,3. Recent efforts focused on the development of more potent TKI that also inhibit mutant tyrosine kinases4,5. However, even effective TKI typically fail to eradicate leukemia-initiating cells6–8, which often cause recurrence of leukemia after initially successful treatment. Here we report on the discovery of a novel mechanism of drug-resistance, which is based on protective feedback signaling of leukemia cells in response to TKI-treatment. We identified BCL6 as a central component of this drug-resistance pathway and demonstrate that targeted inhibition of BCL6 leads to eradication of drug-resistant and leukemia-initiating subclones. BCL6 is a known proto-oncogene that is often translocated in diffuse large B cell lymphoma (DLBCL)9. In response to TKI-treatment, BCR-ABL1 acute lymphoblastic leukemia (ALL) cells upregulate BCL6 protein levels by ~90-fold, i.e. to similar levels as in DLBCL (Fig. 1a). Upregulation of BCL6 in response to TKI-treatment represents a novel defense mechanism, which enables leukemia cells to survive TKI-treatment: Previous work suggested that TKI-mediated cell death is largely p53-independent. Here we demonstrate that BCL6 upregulation upon TKI-treatment leads to transcriptional inactivation of the p53 pathway. BCL6-deficient leukemia cells fail to inactivate p53 and are particularly sensitive to TKI-treatment. BCL6?/? leukemia cells are poised to undergo cellular senescence and fail to initiate leukemia in serial transplant recipients. A combination of TKI-treatment and a novel BCL6 peptide inhibitor markedly increased survival of NOD/SCID mice xenografted with patient-derived BCR-ABL1 ALL cells. We propose that dual targeting of oncogenic tyrosine kinases and BCL6-dependent feedback (Supplementary Fig. 1) represents a novel strategy to eradicate drug-resistant and leukemia-initiating subclones in tyrosine kinase-driven leukemia. PMID:21593872

Duy, Cihangir; Hurtz, Christian; Shojaee, Seyedmehdi; Cerchietti, Leandro; Geng, Huimin; Swaminathan, Srividya; Klemm, Lars; Kweon, Soo-mi; Nahar, Rahul; Braig, Melanie; Park, Eugene; Kim, Yong-mi; Hofmann, Wolf-Karsten; Herzog, Sebastian; Jumaa, Hassan; Koeffler, H Phillip; Yu, J. Jessica; Heisterkamp, Nora; Graeber, Thomas G.; Wu, Hong; Ye, B. Hilda; Melnick, Ari; Muschen, Markus

2011-01-01

252

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

2014-06-18

253

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

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; HIV Infection; Intraocular Lymphoma; Multicentric Castleman Disease; 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; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

2014-09-30

254

Cross-talk between chronic lymphocytic leukemia cells and bone marrow endothelial cells: role of signal transducer and activator of transcription 3.  

PubMed

Chronic lymphocytic leukemia bone marrow is characterized by increased angiogenesis. However, the molecular mediators of neovascularization and the biologic significance of increased endothelial cell proliferation in chronic lymphocytic leukemia require further investigation. Because signal transducer and activator of transcription 3 is constitutively activated in chronic lymphocytic leukemia, we studied the role of signal transducer and activator of transcription 3 in modulating vascular endothelial growth factor expression and the effect of vascular endothelial cells on chronic lymphocytic leukemia cells. Using chromatin immunoprecipitation, we found that anti-signal transducer and activator of transcription 3 antibodies immunoprecipitated DNA of signal transducer and activator of transcription 3, vascular endothelial growth factor, and other signal transducer and activator of transcription 3-regulated genes. In addition, signal transducer and activator of transcription 3-short interfering RNA significantly reduced messenger RNA levels of vascular endothelial growth factor in chronic lymphocytic leukemia cells, suggesting that signal transducer and activator of transcription 3 induces vascular endothelial growth factor expression in chronic lymphocytic leukemia. Remarkably, bone marrow chronic lymphocytic leukemia cells expressed high levels of vascular endothelial growth factor, and high vascular endothelial growth factor levels were detected in the plasma of patients with untreated chronic lymphocytic leukemia and correlated with white blood cell count. Chronic lymphocytic leukemia bone marrow biopsies revealed increased microvascular density and attachment of chronic lymphocytic leukemia cells to endothelial cells. Coculture of chronic lymphocytic leukemia cells and human umbilical vein endothelial cells showed a similar attachment. Furthermore, coculture studies with human umbilical vein endothelial cells showed that human umbilical vein endothelial cells protected chronic lymphocytic leukemia cells from spontaneous apoptosis by direct cell-to-cell contact as assessed by flow cytometry using annexin V. Our data suggest that constitutively activated signal transducer and activator of transcription 3 induces vascular endothelial growth factor production by chronic lymphocytic leukemia cells and that chronic lymphocytic leukemia cells derive a survival advantage from endothelial cells via cell-to-cell contact. PMID:21733558

Badoux, Xavier; Bueso-Ramos, Carlos; Harris, David; Li, Ping; Liu, Zhiming; Burger, Jan; O'Brien, Susan; Ferrajoli, Alessandra; Keating, Michael J; Estrov, Zeev

2011-12-01

255

Synergistic Interactions between HDAC and Sirtuin Inhibitors in Human Leukemia Cells  

PubMed Central

Aberrant histone deacetylase (HDAC) activity is frequent in human leukemias. However, while classical, NAD+-independent HDACs are an established therapeutic target, the relevance of NAD+-dependent HDACs (sirtuins) in leukemia treatment remains unclear. Here, we assessed the antileukemic activity of sirtuin inhibitors and of the NAD+-lowering drug FK866, alone and in combination with traditional HDAC inhibitors. Primary leukemia cells, leukemia cell lines, healthy leukocytes and hematopoietic progenitors were treated with sirtuin inhibitors (sirtinol, cambinol, EX527) and with FK866, with or without addition of the HDAC inhibitors valproic acid, sodium butyrate, and vorinostat. Cell death was quantified by propidium iodide cell staining and subsequent flow-cytometry. Apoptosis induction was monitored by cell staining with FITC-Annexin-V/propidium iodide or with TMRE followed by flow-cytometric analysis, and by measuring caspase3/7 activity. Intracellular Bax was detected by flow-cytometry and western blotting. Cellular NAD+ levels were measured by enzymatic cycling assays. Bax was overexpressed by retroviral transduction. Bax and SIRT1 were silenced by RNA-interference. Sirtuin inhibitors and FK866 synergistically enhanced HDAC inhibitor activity in leukemia cells, but not in healthy leukocytes and hematopoietic progenitors. In leukemia cells, HDAC inhibitors were found to induce upregulation of Bax, a pro-apoptotic Bcl2 family-member whose translocation to mitochondria is normally prevented by SIRT1. As a result, leukemia cells become sensitized to sirtuin inhibitor-induced apoptosis. In conclusion, NAD+-independent HDACs and sirtuins cooperate in leukemia cells to avoid apoptosis. Combining sirtuin with HDAC inhibitors results in synergistic antileukemic activity that could be therapeutically exploited. PMID:21818379

Cea, Michele; Soncini, Debora; Fruscione, Floriana; Raffaghello, Lizzia; Garuti, Anna; Emionite, Laura; Moran, Eva; Magnone, Mirko; Zoppoli, Gabriele; Reverberi, Daniele; Caffa, Irene; Salis, Annalisa; Cagnetta, Antonia; Bergamaschi, Micaela; Casciaro, Salvatore; Pierri, Ivana; Damonte, Gianluca; Ansaldi, Filippo; Gobbi, Marco; Pistoia, Vito; Ballestrero, Alberto; Patrone, Franco

2011-01-01

256

Hairy Root Transformation Using Agrobacterium rhizogenes as a Tool for Exploring Cell Type-Specific Gene Expression and Function Using Tomato as a Model.  

PubMed

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

2014-10-01

257

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.

258

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

2014-06-24

259

Establishment and characterization of a rare atypical chronic myeloid leukemia cell line NT-1.  

PubMed

Human leukemia cell lines are of great value in leukemia research. In this study, we established and described the biological characteristics of a rare atypical chronic myeloid (aCML) leukemia cell line (NT-1). Mononuclear cells were isolated from the bone marrow of a patient with atypical chronic myeloid leukemia (Ph(-)/bcr(-)/abl(-)), and were passaged by liquid culture. Cells were maintained without any cytokines for over 1 year, and named NT-1. This cell line was extensively characterized using morphological assays, flow cytometry, cytogenetic analysis, clonogenic culture, quantitative fluorescent PCR, short tandem repeating sequence PCR (STR-PCR) and array-CGH. Its tumorigenic capacity was also examined in nude mice. The NT-1 cell line had morphological features of chronic myeloid leukemia and major myeloid markers (CD13, CD33, CD11b). Additionally, NT-1 expressed progenitor cells and natural killer cell-related antigens such as CD34, CD117, CD56. Cytogenetic analysis initially demonstrated two abnormalities: 47, xx, +8 and 47, xx, +8 accompanied by t(5;12)(q31;p13) translocation. The one-year passage process did not alter the karyotype. NT-1 cells maintained the same morphology, immunophenotyping and cytogenetic features as primary leukemia cells, which was strongly supported by STR-PCR results. Neither Epstein-Barr virus nor mycoplasma was detected in the NT-1 line. In addition, NT-1 cells showed high tumorigenic capacity in nude mice. NT-1 is a new atypical chronic myeloid leukemia cell line with the +8 and t(5,12) translocation, and exhibits high tumorigenicity in nude mice. This new cell line provides a useful tool for the study of leukemogenesis. PMID:25012564

Qian, Juan; Wang, Qin-Rong; Liu, Jie; Jiang, Sheng-Hua; Ni, Xiao-Qing; Lin, Zeng-Hua; Zhang, Ya-Ping; Liu, Hong

2014-09-01

260

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

261

IgE synthesis by chronic lymphocytic leukemia cells  

PubMed Central

The present results indicate that B cells isolated from chronic lymphocytic leukemia (B-CLL) from 11 of 14 patients are capable of specifically producing IgE upon costimulation with IL-4 and hydrocortisone (HC). IgE is detected by intracytoplasmic fluorescence staining and by RIA. Clinical, hematological, and immunological parameters (including Rai stage, WBC, Lc, sIg kappa/lambda, CD5, and CD23 expression) cannot distinguish the IgE responder from the nonresponder patients. IL-4 alone is a potent inducer of human IgE synthesis by normal PBMC and we show here that its effect is strikingly enhanced by HC. The IgE produced by B-CLLs are monoclonal since they display the same L chain type as the freshly isolated CD5+ B-CLLs. We, therefore, conclude that the combination of IL-4 and HC can abrogate the maturation arrest of CD5+ B-CLLs by inducing their differentiation into IgE-producing cells. The present data provide a unique model to study the isotype switching to IgE and the regulation of human IgE synthesis by monoclonal human B cells. PMID:2478656

1989-01-01

262

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

263

A Case of Systemic Mastocytosis Associated with Acute Myeloid Leukemia Terminating as Aleukemic Mast Cell Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation  

PubMed Central

In up to 40% of systemic mastocytosis (SM) cases, an associated clonal hematological non-mast cell lineage disease such as AML is diagnosed before, simultaneously with, or after the diagnosis of SM. A 40-yr-old man was diagnosed with AML with t(8;21)(q22;q22). Mast cells were not noted at diagnosis, but appeared as immature forms at relapse. After allogeneic hematopoietic stem cell transplantation (HSCT), leukemic myeloblasts were not observed; however, neoplastic metachromatic blasts strikingly proliferated during the state of bone marrow aplasia, and finally, aleukemic mast cell leukemia developed. As the disease progressed, we observed serial morphologic changes from immature mast cells with myeloblasts to only metachromatic blasts and atypical mast cells as mast cell leukemia; FISH analysis showed that the neoplastic mast cells originated from the same clone as the leukemic myeloblasts of AML. PMID:23483057

Bae, Mi Hyun; Kim, Hyun-Ki; Seo, Eul-Ju; Park, Sang Hyuk; Cho, Young-Uk; Jang, Seongsoo; Chi, Hyun-Sook; Lee, Kyu-Hyung

2013-01-01

264

Gefitinib targets ZAP-70-expressing chronic lymphocytic leukemia cells and inhibits B-cell receptor signaling.  

PubMed

Chronic lymphocytic leukemia (CLL) can be divided into groups based on biomarkers of poor prognosis. The expression of the tyrosine kinase ZAP-70 (member of the Syk tyrosine kinase family) in CLL cells is associated with shorter overall survival in CLL patients. Currently, there is a lack of targeted therapies for patients with ZAP-70 expression in CLL cells. The tyrosine kinase inhibitor gefitinib has been shown to be effective at induce apoptosis in acute myeloid leukemia through inhibition of Syk. In this study, we sought to test the efficacy of gefitinib in primary human ZAP-70+ CLL cells. We demonstrate that gefitinib preferentially induces cell death in ZAP-70-expressing CLL cells with a median IC50 of 4.5??M. In addition, gefitinib decreases the viability of ZAP-70+ Jurkat T leukemia cells but fails to affect T cells from CLL patients. Western blot analysis shows gefitinib reduces both basal and B-cell receptor (BCR)-stimulated phosphorylation of Syk/ZAP-70, ERK, and Akt in ZAP-70+ CLL cells. Moreover, gefitinib inhibits the pro-survival response from BCR stimulation and decreases pro-survival proteins such as Mcl-1. Finally, ZAP-70 expression sensitizes Raji cells to gefitinib treatment. These results demonstrate that gefitinib specifically targets ZAP-70+ CLL cells and inhibits the BCR cell survival pathway leading to apoptosis. This represents the likelihood of tyrosine kinase inhibitors being effective targeted treatments for ZAP-70+ CLL cells.Cell Death and Disease (2014) 5, e1439; doi:10.1038/cddis.2014.391; published online 2 October 2014. PMID:25275600

Dielschneider, R F; Xiao, W; Yoon, J-Y; Noh, E; Banerji, V; Li, H; Marshall, A J; Johnston, J B; Gibson, S B

2014-01-01

265

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

266

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. ...

267

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. ...

268

T cell receptor alpha-chain gene rearrangements in B-precursor leukemia are in contrast to the findings in T cell acute lymphoblastic leukemia. Comparative study of T cell receptor gene rearrangement in childhood leukemia.  

E-print Network

We have analyzed T cell receptor alpha-chain gene configuration using three genomic joining (J) region probes in 64 children with acute lymphoblastic leukemia (ALL). 11 out of 18 T-ALLs were T3 positive; alpha-chain gene rearrangements were...

Hara, Junichi; Benedict, Stephen H.; Mak, Tak W.; Gelfand, Erwin W.

1987-12-01

269

Leukemic Stem Cell Frequency: A Strong Biomarker for Clinical Outcome in Acute Myeloid Leukemia  

PubMed Central

Introduction Treatment failure in acute myeloid leukemia is probably caused by the presence of leukemia initiating cells, also referred to as leukemic stem cells, at diagnosis and their persistence after therapy. Specific identification of leukemia stem cells and their discrimination from normal hematopoietic stem cells would greatly contribute to risk stratification and could predict possible relapses. Results For identification of leukemic stem cells, we developed flow cytometric methods using leukemic stem cell associated markers and newly-defined (light scatter) aberrancies. The nature of the putative leukemic stem cells and normal hematopoietic stem cells, present in the same patient's bone marrow, was demonstrated in eight patients by the presence or absence of molecular aberrancies and/or leukemic engraftment in NOD-SCID IL-2R?-/- mice. At diagnosis (n?=?88), the frequency of the thus defined neoplastic part of CD34+CD38- putative stem cell compartment had a strong prognostic impact, while the neoplastic parts of the CD34+CD38+ and CD34- putative stem cell compartments had no prognostic impact at all. After different courses of therapy, higher percentages of neoplastic CD34+CD38- cells in complete remission strongly correlated with shorter patient survival (n?=?91). Moreover, combining neoplastic CD34+CD38- frequencies with frequencies of minimal residual disease cells (n?=?91), which reflect the total neoplastic burden, revealed four patient groups with different survival. Conclusion and Perspective Discrimination between putative leukemia stem cells and normal hematopoietic stem cells in this large-scale study allowed to demonstrate the clinical importance of putative CD34+CD38- leukemia stem cells in AML. Moreover, it offers new opportunities for the development of therapies directed against leukemia stem cells, that would spare normal hematopoietic stem cells, and, moreover, enables in vivo and ex vivo screening for potential efficacy and toxicity of new therapies. PMID:25244440

Terwijn, Monique; Zeijlemaker, Wendelien; Kelder, Angele; Rutten, Arjo P.; Snel, Alexander N.; Scholten, Willemijn J.; Pabst, Thomas; Verhoef, Gregor; Lowenberg, Bob; Zweegman, Sonja; Ossenkoppele, Gert J.; Schuurhuis, Gerrit J.

2014-01-01

270

The emerging roles of Notch signaling in leukemia and stem cells  

PubMed Central

The Notch signaling pathway plays a critical role in maintaining the balance between cell proliferation, differentiation and apoptosis, and is a highly conserved signaling pathway that regulates normal development in a context- and dose-dependent manner. Dysregulation of Notch signaling has been suggested to be key events in a variety of hematological malignancies. Notch1 signaling appears to be the central oncogenic trigger in T cell acute lymphoblastic leukemia (T-ALL), in which the majority of human malignancies have acquired mutations that lead to constitutive activation of Notch1 signaling. However, emerging evidence unexpectedly demonstrates that Notch signaling can function as a potent tumor suppressor in other forms of leukemia. This minireview will summarize recent advances related to the roles of activated Notch signaling in human lymphocytic leukemia, myeloid leukemia, stem cells and stromal microenvironment, and we will discuss the perspectives of Notch signaling as a potential therapeutic target as well. PMID:24252593

2013-01-01

271

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

272

Therapeutic options for adult T-cell leukemia/lymphoma.  

PubMed

Adult T-cell leukemia/lymphoma (ATL) is the first human malignancy associated with a retroviral infection and occurs in approximately 5 % of the 15 million to 20 million people infected by human T-cell lymphotropic virus 1. In general, ATL is resistant to chemotherapy, and while awaiting new therapeutics, patients commonly face a detrimental progress of the disease and death. The viral oncoprotein Tax is a key player in the cause of ATL and acts by interfering with DNA repair, cell cycle, apoptosis, and proliferative cellular programs. The Shimoyama classification describes four different subtypes (acute, lymphoma, chronic, and smoldering) associated with different outcomes, and that require different treatment strategies tailored to the clinical presentation. In aggressive ATL (acute and lymphoma subtypes), clinical trials, mostly from Japan, have demonstrated that combinations of chemotherapy can induce acceptable response rates, especially in the lymphoma subtype. However, the overall outcome remains extremely poor owing to a high rate of relapse. Similarly, the so-called indolent forms (smoldering and chronic subtypes) have a poor outcome whether they are managed with watching and waiting or treated with chemotherapy. We recently realized a worldwide meta-analysis and showed that the combination of zidovudine and interferon alpha is highly effective in the leukemic subtypes of ATL and should be considered as standard first-line therapy in that setting. This combination has changed the natural history of the disease through achievement of significantly improved long-term survival in patients with smoldering and chronic ATL as well as a subset of patients with acute ATL. Patients with lymphoma-type ATL still benefit from chemotherapy induction with concurrent or sequential antiretroviral therapy with zidovudine and interferon alpha. Allogeneic stem cell transplantation is a promising option but has several barriers. New drugs such as the new antibody anti-CXCR4 show promising results. Prospective trials testing maintenance therapy in order to avoid relapse are warranted when the patient cannot undergo allogeneic stem cell transplantation. PMID:23943384

Marçais, Ambroise; Suarez, Felipe; Sibon, David; Frenzel, Laurent; Hermine, Olivier; Bazarbachi, Ali

2013-10-01

273

Emodin Induces Apoptotic Death in Murine Myelomonocytic Leukemia WEHI-3 Cells In Vitro and Enhances Phagocytosis in Leukemia Mice In Vivo  

PubMed Central

Emodin is one of major compounds in rhubarb (Rheum palmatum L.), a plant used as herbal medicine in Chinese population. Although many reports have shown that emodin exhibits anticancer activity in many tumor cell types, there is no available information addressing emodin-affected apoptotic responses in the murine leukemia cell line (WEHI-3) and modulation of the immune response in leukemia mice. We investigated that emodin induced cytotoxic effects in vitro and affected WEHI-3 cells in vivo. This study showed that emodin decreased viability and induced DNA fragmentation in WEHI-3 cells. Cells after exposure to emodin for 24?h have shown chromatin condensation and DNA damage. Emodin stimulated the productions of ROS and Ca2+ and reduced the level of ??m by flow cytometry. Our results from Western blotting suggest that emodin triggered apoptosis of WEHI-3 cells through the endoplasmic reticulum (ER) stress, caspase cascade-dependent and -independent mitochondrial pathways. In in vivo study, emodin enhanced the levels of B cells and monocytes, and it also reduced the weights of liver and spleen compared with leukemia mice. Emodin promoted phagocytic activity by monocytes and macrophages in comparison to the leukemia mice group. In conclusions, emodin induced apoptotic death in murine leukemia WEHI-3 cells and enhanced phagocytosis in the leukemia animal model. PMID:21660305

Chang, Yuan-Chang; Lai, Tung-Yuan; Yu, Chun-Shu; Chen, Hung-Yi; Yang, Jai-Sing; Chueh, Fu-Shin; Lu, Chi-Cheng; Chiang, Jo-Hua; Huang, Wen-Wen; Ma, Chia-Yu; Chung, Jing-Gung

2011-01-01

274

Elevated expression of pleiotrophin in lymphocytic leukemia CD19(+) B cells.  

PubMed

Pleiotrophin (PTN) has been demonstrated to be strongly expressed in many fetal tissues, but seldom in healthy adult tissues. While PTN has been reported to be expressed in many types of tumors as well as at high serum concentrations in patients with many types of cancer, to date, there has been no report that PTN is expressed in leukemia, especially in lymphocytic leukemia. We isolated the CD19(+) subset of B cells from peripheral blood from healthy adults, B-cell acute lymphocytic leukemia (B-ALL) patients, and B-cell chronic lymphocytic leukemia (B-CLL) patients and examined these cells for PTN mRNA and protein expression. We used immunocytochemistry, western blotting, and enzyme-linked immunosorbent assay to show that PTN protein is highly expressed in CD19(+) B cells from B-ALL and B-CLL patients, but barely expressed in B cells from healthy adults. We also examined PTN expression at the nucleic acid level using reverse transcription polymerase chain reaction (RT-PCR) and northern blotting and detected a high levels of PTN transcripts in the CD19(+) B cells from both groups of leukemia patients, but very few in the CD19(+) B cells from the healthy controls. Interestingly, the quantity of the PTN transcripts correlated with the severity of disease. Moreover, suppression of PTN activity with an anti-PTN antibody promoted apoptosis of cells from leukemia patients and cell lines SMS-SB and JVM-2. This effect of the anti-PTN antibody suggests that PTN may be a new target for the treatment of lymphocytic leukemia. PMID:24698102

Du, Chun-Xian; Wang, Lan; Li, Yan; Xiao, Wei; Guo, Qin-Lian; Chen, Fei; Tan, Xin-Ti

2014-10-01

275

Use of Recombinant Cell Permeable Small Peptides to Modulate Glucocorticoid Sensitivity of Acute Lymphoblastic Leukemia Cells  

PubMed Central

Glucocorticoid (GC) hormones induce apoptosis in T-cell and pre-B-cell acute lymphoblastic leukemia (ALL) cells. Steroid-mediated apoptosis requires a threshold level of the glucocorticoid receptor (GR) protein, and increasing the intracellular GR levels in ALL cells would augment their hormone-sensitivity. A protein transduction domain (PTD) approach was used to accomplish this. We produced an HIV Tat PTD domain fusion protein (Tat-GR554-777) that potentially competes for the degradation of GR protein by the ubiquitin-proteasome system and should thus increase its intracellular levels by “stabilizing” the GR. We also designed a fusion peptide for the c-Myb DNA binding domain, Tat-c-Myb DBD, since the biological function of this peptide as a dominant negative inhibitor of the c-Myb protein was already known. Purified, bacterially expresssed Tat-c-Myb DBD and Tat-GR554-777 exhibited highly efficient transduction into cultured ALL cell lines including 697 (pre-B-ALL) and CEM-C7 (T-ALL) cells. As expected, the transduced Tat-c-Myb DBD peptide inhibited steroid-mediated stimulation of a GR promoter-luciferase reporter gene. Significantly, transduced Tat-GR554-777 effectively increased intracellular GR levels in the GC resistant T-ALL cell line, CEM-C1, and in the pre-B-ALL 697 cell line. Furthermore, transduction of Tat-GR554-777 rendered GC-resistant CEM-C1 cells sensitive to steroid killing and further sensitized 697 cells to steroid. The use of Tat-fusion peptide transduction may eventually lead to innovative therapeutic modalities to improve the clinical response of patients suffering from T-cell and pre-B-cell acute lymphoblastic leukemia by increasing steroid-responsiveness and perhaps converting steroid-resistant leukemia to a hormone-responsive phenotype. PMID:20831260

Geng, Chuan-dong; Vedeckis, Wayne V.

2010-01-01

276

Anti-Leukemia Activity of In Vitro-Expanded Human Gamma Delta T Cells in a Xenogeneic Ph+ Leukemia Model  

PubMed Central

Gamma delta T cells (GDTc) lyse a variety of hematological and solid tumour cells in vitro and in vivo, and are thus promising candidates for cellular immunotherapy. We have developed a protocol to expand human GDTc in vitro, yielding highly cytotoxic Vgamma9/Vdelta2 CD27/CD45RA double negative effector memory cells. These cells express CD16, CD45RO, CD56, CD95 and NKG2D. Flow cytometric, clonogenic, and chromium release assays confirmed their specific cytotoxicity against Ph+ cell lines in vitro. We have generated a fluorescent and bioluminescent Ph+ cell line, EM-2eGFPluc, and established a novel xenogeneic leukemia model. Intravenous injection of EM-2eGFPluc into NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice resulted in significant dose-dependent bone marrow engraftment; lower levels engrafted in blood, lung, liver and spleen. In vitro-expanded human GDTc injected intraperitoneally were found at higher levels in blood and organs compared to those injected intravenously; GDTc survived at least 33 days post-injection. In therapy experiments, we documented decreased bone marrow leukemia burden in mice treated with GDTc. Live GDTc were found in spleen and bone marrow at endpoint, suggesting the potential usefulness of this therapy. PMID:21304898

Siegers, Gabrielle M.; Felizardo, Tania C.; Mathieson, A. Mark; Kosaka, Yoko; Wang, Xing-Hua; Medin, Jeffrey A.; Keating, Armand

2011-01-01

277

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

278

Induction of Adult T-Cell Leukemia-Like Lymphoproliferative Disease and Its Inhibition by Adoptive Immunotherapy in T-Cell-Deficient Nude Rats Inoculated with Syngeneic Human T-Cell Leukemia Virus Type 1-Immortalized Cells  

Microsoft Academic Search

Human T-cell leukemia virus type 1 (HTLV-1) has been shown to be the etiologic agent of adult T-cell leukemia (ATL), but the in vivo mechanism by which the virus causes the malignant transformation is largely unknown. In order to investigate the mechanisms of HTLV-1 leukemogenesis, we developed a rat model system in which ATL-like disease was reproducibly observed, following inoculation

TAKASHI OHASHI; SHINO HANABUCHI; HIROTOMO KATO; YOSHIHIRO KOYA; FUMIYO TAKEMURA; KATSUIKU HIROKAWA; TAKASHI YOSHIKI; YUETSU TANAKA; MASAHIRO FUJII; MARI KANNAGI

279

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.; Cante-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

280

Productive Infection and Cell-Free Transmission of Human T-Cell Leukemia Virus in a Nonlymphoid Cell Line  

Microsoft Academic Search

Human T-cell leukemia virus (HTLV), American PL isolate, was transmitted by cocultivation and by cell-free filtrates to a nonlymphoid human osteogenic sarcoma (HOS) cell line, designated HOS\\/PL, but not to nine other lines bearing receptors for HTLV. HOS and HOS\\/PL cells are not dependent on interleukin-2 and do not express interleukin-2 receptors that are recognized by anti-Tac monoclonal antibody. HTLV

P. Clapham; K. Nagy; R. Cheingsong-Popov; M. Exley; R. A. Weiss

1983-01-01

281

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

282

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 ...

283

Acute 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, however, the bone marrow produces abnormal white blood ...

284

Intratesticular Transplantation of Testicular Cells from Leukemic Rats Causes Transmission of Leukemia1  

Microsoft Academic Search

A rat T-cell leukemia model was used to study the safety of germ cell transplantation as a mean of preventing infertility in males undergoing gonadotoxic cancer treatment. Donor germ cells were harvested from the testes of terminally ill leukemic rats and were either used directly or cryopreserved and thawed before transplantation by rete testis microin- jection. All rats transplanted with

Kirsi Jahnukainen; Mi Hou; Cecilia Petersen; Brian Setchell; Olle Soder

285

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 oxygen species (ROS) were generated in BA-treated cells. BA-induced differentiation was accompanied. In addition, migratory and invasive properties of HL-60 cells were enhanced by BA, but differently affected

Paris-Sud XI, Université de

286

Induction of apoptosis in leukemia cell lines by Linum persicum and Euphorbia cheiradenia  

Microsoft Academic Search

Purpose: In the present study two medicinal herbs Linum persicum and Euphorbia cheiradenia that are native to Iran were tested for their possible anticancer effect and induction of apoptosis on human tumor cell lines including leukemia cell lines. Methods: The effect of methanolic extracts of the herbs on the inhibition of cell proliferation was assessed by MTT colorimetric assay. K562

Zahra Amirghofran; Masoud Bahmani; Abbas Azadmehr; Katayoun Javidnia

2006-01-01

287

Ipilimumab and Rituximab In Treating Patients With Relapsed or Refractory B-Cell Lymphoma  

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; 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

2014-11-25

288

Selective T Cell Depletion in Preventing Graft-Versus-Host Disease in Patients With Acute Lymphocytic Leukemia, Acute Myeloid Leukemia, or Chronic Myelogenous Leukemia Undergoing Donor Peripheral Blood 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); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Graft Versus Host Disease; 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; Relapsing Chronic Myelogenous Leukemia

2014-09-03

289

Farnesyltransferase inhibitor tipifarnib inhibits Rheb prenylation and stabilizes Bax in acute myelogenous leukemia cells  

PubMed Central

Although farnesyltransferase inhibitors have shown promising activity in relapsed lymphoma and sporadic activity in acute myelogenous leukemia, their mechanism of cytotoxicity is incompletely understood, making development of predictive biomarkers difficult. In the present study, we examined the action of tipifarnib in human acute myelogenous leukemia cell lines and clinical samples. In contrast to the Ras/MEK/ERK pathway-mediated Bim upregulation that is responsible for tipifarnib-induced killing of malignant lymphoid cells, inhibition of Rheb-induced mTOR signaling followed by dose-dependent upregulation of Bax and Puma occurred in acute myelogenous leukemia cell lines undergoing tipifarnib-induced apoptosis. Similar Bax and Puma upregulation occurred in serial bone marrow samples harvested from a subset of acute myelogenous leukemia patients during tipifarnib treatment. Expression of FTI-resistant Rheb M184L, like knockdown of Bax or Puma, diminished tipifarnib-induced killing. Further analysis demonstrated that increased Bax and Puma levels reflect protein stabilization rather than increased gene expression. In U937 cells selected for tipifarnib resistance, neither inhibition of signaling downstream of Rheb nor Bax and Puma stabilization occurred. Collectively, these results not only identify a pathway downstream from Rheb that contributes to tipifarnib cytotoxicity in human acute myelogenous leukemia cells, but also demonstrate that FTI-induced killing of lymphoid versus myeloid cells reflects distinct biochemical mechanisms downstream of different farnesylated substrates. (ClinicalTrials.gov identifier NCT00602771) PMID:23996484

Ding, Husheng; McDonald, Jennifer S.; Yun, Seongseok; Schneider, Paula A.; Peterson, Kevin L.; Flatten, Karen S.; Loegering, David A.; Oberg, Ann L.; Riska, Shaun M.; Huang, Shengbing; Sinicrope, Frank A.; Adjei, Alex A.; Karp, Judith E.; Meng, X. Wei; Kaufmann, Scott H.

2014-01-01

290

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

291

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

2014-10-06

292

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

293

Inverse relationship of tumors and mononuclear cell leukemia infiltration in the lungs of F344 rats  

SciTech Connect

In 1970 and F344 rat, along with the B6C3F{sub 1} mouse, were selected as the standard rodents for the National Cancer Institute Carcinogenic Bioassay program for studies of potentially carcinogenic chemicals. The F344 rat has also been used in a variety of other carcinogenesis studies, including numerous studies at ITRI. A major concern to be considered in evaluating carcinogenic bioassay studies using the F344 rat is the relatively high background incidence of mononuclear cell leukemia (MCL) (also referred to as large granular lymphocytic leukemia, Fischer rat leukemia, or monocytic leukemia). Incidences of MCL ranging from 10 to 72% in male F344 rats to 6 to 31% in female F344 rats have been reported. Gaining the understanding of the mechanisms involved in the negative correlations noted should enhance our understanding of the mechanisms involved in the development of lung cancer.

Lundgren, D.L.; Griffith, W.C.; Hahn, F.F.

1995-12-01

294

Loss of the ex vivo but not the reinducible CD8+ T-cell response to Tax in human T-cell leukemia virus type 1-infected patients with adult T-cell leukemia\\/lymphoma  

Microsoft Academic Search

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia\\/lymphoma (ATLL) and HTLV-1-associated myelopathy (HAM). In asymptomatic carriers and HAM patients, HTLV-1 infection leads to a vigorous cytotoxic T-cell (CTL) response mainly directed to the regulatory Tax protein. In contrast, initial studies showed that anti-HTLV-1 CTL activities were not reproductively detected in ATLL patients, neither ex vivo, nor after

B Arnulf; M Thorel; Y Poirot; R Tamouza; E Boulanger; A Jaccard; E Oksenhendler; O Hermine; C Pique

2004-01-01

295

Prevention of Adult T-Cell Leukemia-Like Lymphoproliferative Disease in Rats by Adoptively Transferred T Cells from a Donor Immunized with Human T-Cell Leukemia Virus Type 1 Tax-Coding DNA Vaccine  

Microsoft Academic Search

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) in infected individuals after a long incubation period. To dissect the mechanisms of the development of the disease, we have previously established a rat model of ATL-like disease which allows examination of the growth and spread of HTLV-1 infected tumor cells, as well assessment of the effects of

TAKASHI OHASHI; SHINO HANABUCHI; HIROTOMO KATO; HIROMI TATENO; FUMIYO TAKEMURA; TOMONORI TSUKAHARA; YOSHIHIRO KOYA; ATSUHIKO HASEGAWA; TAKAO MASUDA; MARI KANNAGI

2000-01-01

296

Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma  

ClinicalTrials.gov

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

2014-11-15

297

Low CD4\\/CD8 T-Cell Ratio Associated with Inflammatory Arthropathy in Human T-Cell Leukemia Virus Type I Tax Transgenic Mice  

Microsoft Academic Search

BackgroundHuman T-cell leukemia virus type I (HTLV-1) can cause an aggressive malignancy known as adult T-cell leukemia\\/lymphoma (ATL) as well as inflammatory diseases such as HTLV-1-associated myelopathy\\/tropical spastic paraparesis (HAM\\/TSP). A transgenic mouse that expresses HTLV-1 Tax also develops T-cell leukemia\\/lymphoma and an inflammatory arthropathy that resembles rheumatoid arthritis. The aim of this study was to identify the primary T-cell

Takeo Ohsugi; Toshio Kumasaka

2011-01-01

298

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

299

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

2014-05-23

300

A Human Leukemia Cell with Both B and T Cell Surface Receptors  

PubMed Central

Bone-marrow-derived (B) and thymus-derived (T) lymphocytes can be distinguished by the presence of a number of receptors and differentiation antigens. The presence of these markers has facilitated the identification and characterization of the mononuclear cells in a number of animal and human lymphoid malignancies. We describe here the immunological properties of human leukemia cells that are highly unusual, since they simultaneously bear the receptor for sheep erythrocytes characteristic of human T lymphocytes and the receptor for antigen-antibody-complement complexes characteristic of human B lymphocytes. A small number (about 2%) of normal human lymphocytes bearing both of these receptors was also identified. Images PMID:4274561

Shevach, E.; Edelson, R.; Frank, M.; Lutzner, M.; Green, I.

1974-01-01

301

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

302

Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus  

Microsoft Academic Search

The aim of this project was to identify situations where allogeneic stem cell transplantation (allo-SCT) might be considered as a preferred treatment option for patients with B-cell chronic lymphocytic leukemia (CLL). Based on a MEDLINE search and additional sources, a consented proposal was drafted, refined and approved upon final discussion by an international expert panel. Key elements of the consensus

P Dreger; P Corradini; E Kimby; M Michallet; D Milligan; J Schetelig; W Wiktor-Jedrzejczak; D Niederwieser; M Hallek; E Montserrat

2007-01-01

303

Identification of a novel SEPT9-ABL1 fusion gene in a patient with T-cell prolymphocytic leukemia  

PubMed Central

T-cell prolymphocytic leukemia (T-PLL), a rare type of peripheral T-cell leukemia, is characterized by marked splenomegaly with rapidly progressive lymphocytosis and a poor prognosis. Nine kinds of ABL1 chimeric genes have been identified in various kinds of hematological malignancies, such as chronic myeloid leukemia and B- or T-lymphoblastic leukemia. However, there have been no reports describing T-PLL cases with ABL1 rearrangements. We herein report a case of T-PLL with a novel SEPT9-ABL1 fusion gene which induced strong resistance to tyrosine kinase inhibitors such as imatinib and dasatinib. PMID:25068103

Suzuki, Rikio; Matsushita, Hiromochi; Kawai, Hidetsugu; Matsuzawa, Hideyuki; Tsuboi, Kosuke; Watanabe, Shigeki; Kawada, Hiroshi; Ogawa, Yoshiaki; Ando, Kiyoshi

2014-01-01

304

Importance of glutamine metabolism in leukemia cells by energy production through TCA cycle and by redox homeostasis.  

PubMed

Some cancer cells depend on glutamine despite of pronounced glycolysis. We examined the glutamine metabolism in leukemia cells, and found that HL-60 cells most depended on glutamine in the 4 acute myelogenous leukemia (AML) cell lines examined: growth of HL-60 cells was most suppressed by glutamine deprivation and by inhibition of glutaminolysis, which was rescued by tricarboxylic acid (TCA) cycle intermediate, oxaloacetic acid. Glutamine is also involved in antioxidant defense function by increasing glutathione. Glutamine deprivation suppressed the glutathione content and elevated reactive oxygen species most evidently in HL-60 cells. Glutamine metabolism might be a therapeutic target in some leukemia. PMID:24762082

Goto, Mineaki; Miwa, Hiroshi; Shikami, Masato; Tsunekawa-Imai, Norikazu; Suganuma, Kazuto; Mizuno, Shohei; Takahashi, Miyuki; Mizutani, Motonori; Hanamura, Ichiro; Nitta, Masakazu

2014-07-01

305

Stereotypical Chronic Lymphocytic Leukemia B-Cell Receptors Recognize Survival Promoting Antigens on Stromal Cells  

PubMed Central

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Survival of CLL cells depends on their close contact with stromal cells in lymphatic tissues, bone marrow and blood. This microenvironmental regulation of CLL cell survival involves the stromal secretion of chemo- and cytokines as well as the expression of adhesion molecules. Since CLL survival may also be driven by antigenic stimulation through the B-cell antigen receptor (BCR), we explored the hypothesis that these processes may be linked to each other. We tested if stromal cells could serve as an antigen reservoir for CLL cells, thus promoting CLL cell survival by stimulation through the BCR. As a proof of principle, we found that two CLL BCRs with a common stereotyped heavy chain complementarity-determining region 3 (previously characterized as “subset 1”) recognize antigens highly expressed in stromal cells – vimentin and calreticulin. Both antigens are well-documented targets of autoantibodies in autoimmune disorders. We demonstrated that vimentin is displayed on the surface of viable stromal cells and that it is present and bound by the stereotyped CLL BCR in CLL-stroma co-culture supernatant. Blocking the vimentin antigen by recombinant soluble CLL BCR under CLL-stromal cell co-culture conditions reduces stroma-mediated anti-apoptotic effects by 20–45%. We therefore conclude that CLL BCR stimulation by stroma-derived antigens can contribute to the protective effect that the stroma exerts on CLL cells. This finding sheds a new light on the understanding of the pathobiology of this so far mostly incurable disease. PMID:21209908

Binder, Mascha; Lechenne, Barbara; Ummanni, Ramesh; Scharf, Christan; Balabanov, Stefan; Trusch, Maria; Schluter, Hartmut; Braren, Ingke; Spillner, Edzard; Trepel, Martin

2010-01-01

306

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

307

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

2014-07-03

308

PDZ domain-binding motif of human T-cell leukemia virus type 1 Tax oncoprotein augments the transforming activity in a rat fibroblast cell line  

Microsoft Academic Search

While human T-cell leukemia virus type 1 (HTLV-1) is associated with the development of adult T-cell leukemia (ATL), HTLV-2 has not been reported to be associated with such malignant leukemias. HTLV-1 Tax1 oncoprotein transforms a rat fibroblast cell line (Rat-1) to form multiple large colonies in soft agar, and this activity is much greater than that of HTLV-2 Tax2. We

Akira Hirata; Masaya Higuchi; Akiko Niinuma; Minako Ohashi; Masaya Fukushi; Masayasu Oie; Tetsu Akiyama; Yuetsu Tanaka; Fumitake Gejyo; Masahiro Fujii

2004-01-01

309

Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma  

ClinicalTrials.gov

Contiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

2014-10-28

310

Invariant natural killer T cells reconstitution and the control of leukemia relapse in pediatric haploidentical hematopoietic stem cell transplantation  

PubMed Central

CD1d-restricted invariant (i)NKT cells are innate-like, lipid-reactive T lymphocytes implicated in the control of infections, cancer and autoimmunity. Our study suggests that the reconstitution of the peripheral iNKT cell compartment, following HLA-haploidentical hematopoietic stem cell transplantation, associates with leukemia control in children affected by different hematological malignancies. PMID:22737613

Casorati, Giulia; de Lalla, Claudia; Dellabona, Paolo

2012-01-01

311

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

312

What Is Acute Lymphocytic Leukemia (ALL)?  

MedlinePLUS

... about acute lymphocytic leukemia? What is acute lymphocytic leukemia? Acute lymphocytic leukemia (ALL), also called acute lymphoblastic ... germs by surrounding and digesting them. Development of leukemia Any type of early blood-forming cell of ...

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

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

315

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

316

Hematopoietic stem cell transplantation for treatment of patients with leukemia concomitant with active tuberculosis infection.  

PubMed

Background Currently, hematopoietic stem cell transplantation is still an essential treatment approach for leukemia. However, patients with leukemia often have weakened immune function, especially more seriously compromised cellular immune response, and appear to be at greater risk for tuberculosis infection during the transplantation process. We aimed to investigate the efficacy and safety of hematopoietic stem cell transplantation for the treatment of patients with leukemia accompanying active tuberculosis infection. Material and Methods We retrospectively analyzed records of 7 consecutive patients who were diagnosed with leukemia concomitant with active tuberculosis infection and who underwent hematopoietic stem cell transplantation in our hospital from January 2006 to December 2012. Results Among these 7 patients (4 males and 3 females; median age: 38 years; range: 30-46 years), the mean duration of anti-TB treatment before transplantation was 3 months (range: 2-4.5 months). All patients acquired engraftment, with an implantation rate of 100%. After transplantation, the mean duration of anti-TB treatment was 12 months. All patients had response after receiving anti-TB treatment. One patient died of leukemia relapse 6 months after the transplantation, but no tuberculosis infection-related death was reported. Conclusions Patients with leukemia concomitant with active tuberculosis infection can be treated with hematopoietic stem cell transplantation if they receive an effective anti-TB treatment regimen. The anti-TB treatment regimen had no effect against hematopoietic stem cell transplantation and was well-tolerated. All post-transplanted patients experienced no relapse of tuberculosis during the immune-suppression period. The findings in the present investigation deserve further in-depth study. PMID:25433702

Liu, Mingjuan; Yang, Caie; Liu, Lihui; Shi, Bing; Hu, Wenqing; Ye, Liping; Zhang, Yongqing

2014-01-01

317

Matrix metalloproteinases expression in HL60 promyelocytic leukemia cells during apoptosis  

Microsoft Academic Search

Human promyelocytic leukemia HL-60 cells have been used as a model to study both the expression of matrix-metalloproteinases and the mechanisms of programmed cell death. In the present study we examined the expression of these proteases in HL-60 cells stimulated by different apoptotic triggers. As shown by zymography, HL-60 cells released three major isofroms of the matrix-degrading proteases; when the

G. Gazzanelli; F. Luchetti; S. Burattini; F. Mannello; E. Falcieri; S. Papa

2000-01-01

318

Comparison of infection frequencies in fetus by maternal ascitic cancer and leukemia cells  

Microsoft Academic Search

It was demonstrated that maternal Ehrlich cells could infect fetus in a mouse model, which is another kind of the cancer cells\\u000a inducing cancer ccll infection between mother and fetus besides leukemia L615 cells reported previously by the authors. Among\\u000a the fetus in a pregnancy only a few of them might be infected by the maternal cancer cells. The early

Yongshan Yan; Shang Feng; Yonghong Wang; Ting Zhang

1998-01-01

319

Quantitative Assay of Human T-Cell Leukemia\\/Lymphoma Virus Transformation1  

Microsoft Academic Search

The in vitro transformation of normal T-lymphocytes by human I -cell leukemia\\/lymphoma virus (HTLV-I) is possible utilizing cocultivation techniques. We now report on a quantitative assay for HTLV-I transfor mation. Transformed cell lines were produced by cocultivation of either preactivated (phytohemagglutinin and T-cell growth factor) or nonacti- vated peripheral blood mononuclear cells with an equal number of lethally irradiated HTLV-I-positive

Stephen L. Graziano; Stuart A. Meri; Garth D. Ehrlich; Janet L. Moore; Frederick R. Davey; John Vournakis; J. VJ

320

DNA Fusion Vaccines Induce Epitope-Specific Cytotoxic CD8+ T Cells against Human Leukemia-Associated Minor Histocompatibility Antigens  

Microsoft Academic Search

The graft-versus-leukemia effect of allogeneic stem-cell transplantation is believed to be mediated by T-cell recogni- tion of minor histocompatibility antigens on recipient cells. For minor histocompatibility antigens HA-1 and HA-2, normal cell expression is restricted to hemopoietic cells, and boost- ing the immune response to these antigens may potentiate graft-versus-leukemia effect without accompanying graft- versus-host disease. To increase efficacy, expansion

Jason Rice; Stuart Dunn; Karen Piper; Sarah L. Buchan; Paul A. Moss

321

Precursor B-cell acute lymphoblastic leukemia presenting as obstructive jaundice: a case report  

PubMed Central

Introduction Acute leukemias very rarely present with jaundice. Herein we report a case of precursor B-cell acute lymphoblastic leukemia that presented with jaundice in an adult. Case presentation A 44-year-old Hispanic man presented with right upper quadrant abdominal pain and jaundice. His initial blood work revealed pancytopenia and hyperbilirubinemia. Direct bilirubin was more than 50% of the total. His imaging studies were unremarkable except for hepatomegaly. All blood screening tests for various hepatocellular etiologies were normal. A diagnosis of precursor B-cell acute lymphoblastic leukemia was made upon liver biopsy. It also showed lymphocytic infiltration of the hepatic parenchyma leading to bile stasis. The diagnosis was subsequently confirmed upon bone marrow biopsy. The patient was treated with a hyperfractionated cyclophosphamide/vincristine/doxorubicin/dexamethasone regimen. Conclusion Acute lymphoblastic leukemia should be one of the differential diagnoses that should be considered when initial work-up for jaundice is inconclusive. Some cases of acute lymphoblastic leukemia have been reported in both adults and children to have presented with the initial manifestation of jaundice, but only a few had no radiographic evidence of biliary obstruction. Such presentation can pose a serious diagnostic dilemma for clinicians. This manuscript attempts to highlight it. Moreover, we believe that if acute lymphoblastic leukemia presentations similar to this case continue to be reported in adults or children, a specific immunophenotypic expression and cytogenetic abnormality may be found to be associated with hepatic infiltration by leukemia. This may substantially contribute to the further understanding of the pathophysiology of this hematologic disease. PMID:21722379

2011-01-01

322

Chronic leukemia.  

PubMed

The chronic leukemias include chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). CML is a clonal myeloproliferative hematopoietic stem-cell disorder, and CLL is a monoclonal B-cell disorder. CML is Philadelphia chromosome positive. There are 3 phases of CML: the chronic phase, the accelerated phase, and the blast phase. The primary treatment of CML consists of tyrosine kinase inhibitors. CLL can present as indolent or fulminant disease. Early disease is managed with observation. Fulminant disease is currently treated with alkylating agents, purine analogues, and monoclonal antibodies, but new biotarged therapies are being developed. PMID:24267282

Greenberg, Edythe M Lyn; Probst, Alexandra

2013-12-01

323

Spreading of acute myeloid leukemia cells by trafficking along the peripheral outflow pathway of cerebrospinal fluid.  

PubMed

Acute myeloid leukemia (AML) can affect not only bone marrow (BM) and peripheral blood (PB), but also the compartment of cerebrospinal fluid (CSF). Besides standard chemotherapy, specific and non-specific immunotherapy has been employed synergistically to treat AML patients. Here we report on a patient who received standard chemotherapy, unspecific immunotherapy with interleukin-2, as well as later specific CD8+ T-cell stimulation by RHAMM-R3 peptide vaccination. The patient maintained a complete remission in BM and PB, while he developed recurrent relapses in the CSF. Moreover, the patient developed a chloroma in the vicinity of neuronal sheaths during hematological CR, but high leukemia cell numbers within the CSF spaces over a long time period. This rare observation demonstrates several aspects. There is a previously unknown site of leukemia cell distribution, namely the peripheral cerebrospinal outflow pathway (PCOP). This demonstrates the ineffective therapy of this previously unknown mechanism of leukemia cell spread. The hypothesis that the PCOP is a site of physiological CSF-T-cell trafficking, and the lumen of the PCOP should be considered as an extension of the subarachnoidal spaces without closed anatomical borders is supported by this observation. The CSF spaces, but possibly specifically the PCOP, may represent a previously unknown survival niche of tumor cells within intrathecal spaces. PMID:21737662

Schmitt, Michael; Neubauer, Andreas; Greiner, Jochen; Xu, Xun; Barth, Thomas F E; Bechter, Karl

2011-06-01

324

Leukemia inhibitory factor (LIF) enhances germ cell differentiation from primate embryonic stem cells.  

PubMed

Recently, several research groups have shown that germ cells can be produced in vitro from pluripotent embryonic stem cells (ESCs). In the mouse, live births of offspring using germ cells induced from ESCs in vitro have been reported. Furthermore, some efficient methods for inducing the useful number of germ cells from ESCs have also been developed. On the other hand, in primates, despite the appearances of germ cell-like cells including meiotic cells were observed by spontaneous differentiation or introducing transgenes, it has not been determined whether fully functional germ cells can be derived from ESCs. To elucidate the property for the germ cells induced from primate ESCs, specification of the promoting factors for the germ cell development and improving the efficiency of germ cell derivation are essential. Leukemia inhibitory factor (LIF) has been reported as one of the important factors for mouse primordial germ cell (PGC) survival in vitro. However, the effects of LIF on germ cell formation from pluripotent cells of primates have not been examined. The aim of this study is to determine whether LIF addition can improve in vitro germ cell production from cynomolgus monkey ESCs (cyESCs). After 8 days of differentiation, LIF added culture induced dome-shaped germ cell colonies as indicated by the intense expression of alkaline phosphatase activity (ALP). These cells also demonstrate high-level expression of the germ cell-marker VASA, OCT-4, and BLIMP-1, and show SSEA-1 expression that supports their early stage germ cell identity. Finally, we observed that adding LIF to differentiating cultures inhibited meiotic gene expressions and increased the percentage of ALP-positive cells, and demonstrate that the addition of LIF to differentiation media increases differentiation of early germ cells from the cyESCs. PMID:20698776

Fukunaga, Naoto; Teramura, Takeshi; Onodera, Yuta; Takehara, Toshiyuki; Fukuda, Kanji; Hosoi, Yoshihiko

2010-08-01

325

The Perceived Threat in Adults with Leukemia Undergoing Hematopoietic Stem Cell Transplantation  

PubMed Central

Background: Leukemia and hematopoietic stem cell transplantation (HSCT) create physical, psychological, social, and spiritual distresses in patients. Understanding this threatening situation in adults with leukemia undergoing HSCT will assist health care professionals in providing holistic care to the patients. Objectives: The aim of the present study was exploring the perceived threat in adults with leukemia undergoing HSCT. Patients and Methods: This article is part of a longitudinal qualitative study which used the grounded theory approach and was conducted in 2009-2011. Ten adults with acute leukemia scheduled for HSCT were recruited from the Hematology–Oncology Research Center and Stem Cell Transplantation, Shariati Hospital in Tehran, Iran. A series of pre-transplant and post-transplant in-depth interviews were held in the hospital’s HSCT wards. Totally, 18 interviews were conducted. Three written narratives were also obtained from the participants. The Corbin and Strauss approach was used to analyze the data. Results: Perceived threat was one of the main categories that emerged from the data. This category included four subcategories, "inattention to the signs and symptoms", "doubt and anxiety", "perception of danger and time limitation" and "change of life conditions", which occurred in linear progression over time. Conclusion: Suffering from leukemia and experiencing HSCT are events that are uniquely perceived by patients. This threatening situation can significantly effect perception of patients and cause temporary or permanent alterations in patients' lives. Health care professionals can help these patients by deeper understanding of their experiences and effective interventions.

Farsi, Zahra; Dehghan Nayeri, Nahid; Negarandeh, Reza

2013-01-01

326

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

327

[Chronic lymphatic leukemia. Immunophenotyping as an aid to correct diagnosis].  

PubMed

The purpose of the study was to examine the validity of the primary diagnosis in chronic lymphocytic leukemia based on clinical and morphological criteria, and to examine the role of immune phenotyping for correct diagnosis in an unselected population-based group of patients. Over a 2-year period leukemic cells from 222 of 235 patients in Norway with a recent clinical diagnosis of chronic lymphocytic leukemia (CLL) were immune phenotyped in order to find cases erroneously diagnosed as CLL. Median age was 72.5 years, and the ratio of men to women was 1.47. At the time of diagnosis, 77% of the patients were in Binet stage A and 23% in stage B or C. Immune phenotyping, in some patients followed by lymph node or bone marrow biopsy, showed a different diagnosis in 11 (5%) of 222 patients: prolymphocytic leukemia, four patients (three B-cell and one T-cell); morbus Waldenstrøm, one patient; T-cell CLL, one patient; hairy cell leukemia, one patient; mycosis fungoides, one patient; mantle cell lymphoma, one patient; monocytoid B-cell lymphoma, one patient and immunoblastic lymphoma one patient. In eight of these 11 patients, the clinical features or morphology, or both, were atypical for CLL, but this was not recognized at the time of diagnosis. Thus, immune phenotyping is valuable for correct diagnosis in a small subgroup of patients with chronic B- or T-cell leukemia, and it is essential in patients with modest lymphocytosis (lymphocytes < 10. 10(9)/1). PMID:9485618

Ly, B; Hammerstrøm, J; Bergheim, J; Dahl, I M; Grøttum, K A; Lødemel, B; Baklien, K; Smeland, E

1998-01-20

328

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

PubMed

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 (HSCs) and early T-cell precursor ALL. These results are significant in light of the crucial role of Lmo2 in the maintenance of the HSC. 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

2013-05-01

329

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

2014-08-26

330

Human-fms gene is retained in acute lymphoblastic leukemia cells with del(5)(q32).  

PubMed

Cytogenetic and molecular investigations of NALM 6 cells (a pre-B-lymphoblastic acute leukemia cell line) revealed them to contain both alleles of the c-fms gene, though the cells had chromosomal changes of 5q- and 12p+. The amount of DNA fragments hybridized to the 1.4 kb PstI/PstI v-fms probe in the NALM 6 cells was approximately the same, when compared with cells of an Epstein-Barr virus-transformed lymphoblastoid cell line with a normal karyotype. Chromosome banding analysis revealed that the breakpoint of the 5q- in the NALM 6 cells was at the proximal portion of the 5q32 band. Chromosomal in situ hybridization of NALM 6 cells showed a significant accumulation of grains on the terminal portions of the abnormal 5q- chromosomes (5q32), as well as on the normal chromosomes #5 with a peak at 5q32-q33. These findings indicate that the human c-fms gene is not deleted in the lymphoblastic leukemia cells with a 5q- studied by us and that it does not show rearrangement or amplification. Thus, the results indicate that a difference in the dosage of the c-fms gene in acute lymphoblastic leukemia cells with the 5q- versus that in cells with the 5q- change in nonlymphocytic neoplasia; in the latter a hemizgosity of the c-fms gene has been suggested. PMID:3030533

Ohyashiki, J H; Ohyashiki, K; Sandberg, A A; Minowada, J; Kinniburgh, A J

1987-04-01

331

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

2014-02-17

332

Lenalidomide Induces Immunomodulation in Chronic Lymphocytic Leukemia and Enhances Antitumor Immune Responses Mediated by NK and CD4 T Cells  

PubMed Central

Lenalidomide is an immunomodulatory drug with therapeutic activity in chronic lymphocytic leukemia (CLL). However, it has pleiotropic effects, and the mechanism of action responsible for its therapeutic activity has not been well defined yet. Herein, we show that lenalidomide treatment does not have an effect on the proliferation of leukemia cells, but it increases the proliferation of B cells from healthy donors. Lenalidomide did not exert a direct effect on the apoptosis of leukemia cells obtained from CLL patients, although it indirectly induced their apoptosis through the activation of nonmalignant immune cells. Thus, lenalidomide markedly increased the proliferation of NK and CD4 T cells. The effect of lenalidomide on NK cells was secondary to the induction of IL-2 production by CD4 T cells. Accordingly, depletion of T cells or blockade of IL-2 activity completely abrogated the proliferation of NK cells. Additionally, lenalidomide enhanced NK and NKT-like cell-mediated natural cytotoxicity against leukemia cells from CLL patients. Lenalidomide also upregulated CD20 expression on leukemia cells and, accordingly, it had a synergistic effect with rituximab on promoting antibody-dependent cell-mediated cytotoxicity against primary leukemia cells. Overall, these observations provide a support for combining lenalidomide with rituximab as a treatment in CLL.

Acebes-Huerta, Andrea; Huergo-Zapico, Leticia; Gonzalez-Rodriguez, Ana Pilar; Fernandez-Guizan, Azahara; Payer, Angel R.; Gonzalez, Segundo

2014-01-01

333

Methylation of SFRP5 is related to multidrug resistance in leukemia cells.  

PubMed

Methylation of secreted frizzle-related protein (SFRP) genes activates Wnt/ß-catenin signaling and promotes tumor development. This study investigated whether SFRP5 gene methylation causes multidrug resistance (MDR) in leukemia through the Wnt/ß-catenin signaling, leading to the upregulation of the mdr1 gene and its product, P-glycoprotein (P-gp). Methylation-specific PCR identified SFRP5 gene methylation in cultured bone mononuclear cells from 7/12 patients with acute leukemia and in four human leukemia cell lines (HL-60, Raji, U937 and KG1a). Western blotting revealed absent SFRP5 protein expression in cells from 5/7 patients with SFRP5 gene methylation and in all cell lines. Treatment with a demethylation agent (DAC) rescued SFRP5 expression. mdr1 mRNA and P-gp protein were detected in cells from 3/5 patients with absent SFRP5, and in the KG1a cell line; these cells also had the highest levels of activated ß-catenin. In cells from these three patients, DAC rescued SFRP5 expression and downregulated mdr1 and P-gp. SFRP5 protein expression was rescued in transgenic KG1a/SFRP5 cells, compared with KG1a/eGFP or untransfected KG1a cells. mdr1 and P-gp in KG1a/SFRP5 cells were downregulated. Doxorubicin IC50 values were significantly lower in KG1a/SFRP5 (0.573±0.131 ?M) than in KG1a (0.963±0.115) or KG1a/eGFP (0.917±0.138) cells (P<0.05). We conclude that SFRP5 gene methylation in leukemia cells activates Wnt/ß-catenin signaling to upregulate mdr1/P-gp expression and cause MDR. Recovery of SFRP5 expression reversed MDR in the KG1a leukemia cell line. Our results suggest that modulating SFRP5 methylation could decrease MDR in leukemia patients. PMID:24434572

Wang, H; Wang, X; Hu, R; Yang, W; Liao, A; Zhao, C; Zhang, J; Liu, Z

2014-02-01

334

Comparative Genomic Hybridization Analysis of Natural Killer Cell Lymphoma/Leukemia  

PubMed Central

Putative natural killer (NK) cell lymphoma/leukemia is a rare group of recently characterized hematolymphoid malignancies. They are highly aggressive and frequently present in extranodal sites, including the nasal area and the upper aerodigestive system, and nonnasal areas such as the skin and the gastrointestinal tract. According to clinicopathological features, they can be classified into nasal NK cell lymphoma, nasal-type NK cell lymphoma occurring in nonnasal areas, and NK cell lymphoma/leukemia. Genetic alterations in NK cell lymphoma/leukemia are not well defined. In this study, we have performed comparative genomic hybridization (CGH) on DNA extracted from fresh or frozen tissues of 10 patients with NK cell lymphoma/leukemia. They comprised four nasal NK cell lymphomas, one nasal-type NK cell lymphoma, and five NK cell lymphomas/leukemias. CGH showed frequent deletions at 6q16-q27 (four cases), 13q14-q34 (three cases), 11q22-q25 (two cases), 17p13 (two cases), and loss of the whole chromosome X (two cases). DNA amplification was observed in a majority of the chromosomes. Five cases showed DNA gains at region 1p32-pter. Frequent DNA gains were also found in chromosomes 6p, 11q, 12q, 17q, 19p, 20q, and Xp (three cases each). Interestingly, DNA gains were more frequent in nasal/nasal-type NK cell lymphomas than NK cell lymphoma/leukemia. These genetic alterations correlated well with karyotypic features found in some of the cases. The frequent DNA losses at 6q and 13q suggest that the presence of tumor suppressor genes at these regions is important in NK cell transformation. In addition to establishing novel patterns of genomic imbalances in these rare NK cell malignancies, which may be targets for future molecular analysis, this study also provides important information on genetic alterations in NK cell lymphomas that may be useful in defining their positions in current lymphoma classification schemes, which are increasingly focusing on phenotypic and genotypic correlations. PMID:10550295

Siu, Lisa L. P.; Wong, Kit-Fai; Chan, John K. C.; Kwong, Yok-Lam

1999-01-01

335

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

336

Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations.  

PubMed

The incidence of mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) in de novo acute myeloid leukemia (AML) is approximately 20%. These mutations result in distinct metabolic characteristics including dependency of cancer cells on glutamine as the main source for ?-ketoglutarate, which is consumed by leukemia cells to produce a cancer-derived metabolite, 2-hydroxyglutarate. We sought to exploit this glutamine addiction therapeutically in mutant IDH primary AML cells from patients by measuring cell growth after exposure to a small molecule glutaminase inhibitor, BPTES. We found that BPTES only suppressed the growth of AML cells expressing mutant IDH compared with those expressing wild type IDH. This study lays the groundwork for strategies to target a specific subtype of AML metabolically with IDH mutations with a unique reprogramming of intermediary metabolism that culminates in glutamine dependency of cancer cells for survival. PMID:24333121

Emadi, Ashkan; Jun, Sung Ah; Tsukamoto, Takashi; Fathi, Amir T; Minden, Mark D; Dang, Chi V

2014-04-01

337

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

338

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

339

Cytosine Arabinoside Promotes Cytotoxic Effect of T Cells on Leukemia Cells Mediated by Bispecific Antibody  

PubMed Central

Abstract Chemotherapeutic drugs can enhance an immune response of the host against the tumor in addition to killing cancer cells by direct cytotoxicity. Therefore, the combination of chemotherapy and immunotherapy is a promising approach for eliminating tumors, particularly in advanced stages. A strategic medication is to use a bispecific antibody format that is capable of recruiting polyclonal T cells around antibody-target-expressing tumor cells. Recently, we have constructed a bispecific antibody, anti-CD3×anti-CD19, in a diabody configuration. In this study, we measured B7 family members B7.1 (CD80) and B7.2 (CD86) expressed on a CD19+ human leukemia cell line, Nalm-6, stimulated by cytosine arabinoside (Ara-C). We found that a low concentration of Ara-C could upregulate CD80 expressed on CD19+ Nalm-6 cells. The cytotoxicity of T lymphocytes against Nalm-6 cells in vitro and in vivo mediated by the anti-CD3×anti-CD19 diabody with or without a low dose of Ara-C was compared. The combination of the anti-CD3×anti-CD19 diabody and Ara-C showed the greatest effectiveness in enhancing the cytotoxicity of T cells against the tumor cells in vitro and in vivo. Activated T cells expressed higher levels of CD25 and CD69 and released more interleukin 2. Both perforin/granzyme B system and Fas/FasL pathway were involved in the diabody-induced T-cell cytotoxicity. Moreover, the activated T cells could upregulate ICAM-3 expression on Nalm-6 cells, and inhibition of LFA-1–ICAM-3 interaction impaired cytotoxicity of T cells. It was noted that Ara-C could upregulate CD80 expressed on two of five specimens of acute B lymphoblastic leukemia patient-derived cells. Cytotoxicity of T cells against these two patient-derived cells was enhanced in the presence of the anti-CD3×anti-CD19 diabody. These findings indicate that treatment strategy using both cytotoxic lymphocyte-based immunotherapy and chemotherapy may have synergistic effects. PMID:23879717

Li, Wei; Yang, Ming; Yan, Yan; Shi, RuiZan; Cheng, JunPing; Li, ZhenZhen; Zhang, MengNan; Wang, JianXiang; Xiong, DongSheng

2013-01-01

340

The conformational alteration of the mutated extracellular domain of Fas in an adult T cell leukemia cell line  

Microsoft Academic Search

Fas (APO-1\\/CD95) is a cell surface receptor involved in apoptosis. Almost all adult T cell leukemia (ATL) cells express abundant Fas antigen and show apoptosis induced by IgM anti-Fas monoclonal antibody (mAb). We established the ATL cell line, RSO4, which was obtained from Fas-sensitive ATL cell line SO4 and showed resistance to apoptosis induced by the mAb. By sequencing analysis

Takahiro Maeda; Susumu Nakayama; Yasuaki Yamada; Kazuyuki Sugahara; Hajime Isomoto; Masayuki Tawara; Reishi Yamasaki; Yasuyuki Onimaru; Tetsuro Matsushita; Yoshiyuki Ohzono; Shimeru Kamihira

2002-01-01

341

Short telomeres and high telomerase activity in T-cell prolymphocytic leukemia  

Microsoft Academic Search

To test the role of telomere biology in T-cell prolymphocytic leukemia (T-PLL), a rare aggressive disease characterized by the expansion of a T-cell clone derived from immuno-competent post-thymic T-lymphocytes, we analyzed telomere length and telomerase activity in subsets of peripheral blood leukocytes from 11 newly diagnosed or relapsed patients with sporadic T-PLL. Telomere length values of the leukemic T cells

A Röth; J Dürig; H Himmelreich; S Bug; R Siebert; U Dührsen; P M Lansdorp; G M Baerlocher

2007-01-01

342

Differentiation of Mouse Myeloid Leukemia Cells Induced by 1alpha ,25-dihydroxyvitamin D3  

Microsoft Academic Search

Mouse myeloid leukemia cells can be induced to differentiate into macrophages in vitro by 1alpha ,25-dihydroxyvitamin D3, the active form of vitamin D3. The minimal concentration of 1alpha ,25-dihydroxyvitamin D3 to induce the cell differentiation was 0.12 nM. The degree of cell differentiation in various markers induced by 12 nM 1alpha ,25-dihydroxyvitamin D3 was nearly equivalent to that induced by

Etsuko Abe; Chisato Miyaura; Hiroshi Sakagami; Minoru Takeda; Kunio Konno; Tohru Yamazaki; Shusaku Yoshiki; Tatsuo Suda

1981-01-01

343

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 Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/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 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 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 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; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

2014-10-01

344

Targeted Monoclonal Antibody Therapy for a Rare T-Cell Leukemia  

Cancer.gov

This study will assess the safety of MiK-beta-1, a monoclonal antibody, in patients with T-cell large granular lymphocyte leukemia (T-LGLL). If the treatment is tolerated, it may eventually be used to treat not only T-LGLL, but also certain autoimmune disorders such as rheumatoid arthritis and multiple sclerosis.

345

Immobilization of leukemia inhibitory factor (LIF) to culture murine embryonic stem cells  

Microsoft Academic Search

Murine embryonic stem (ES) cells were cultured on a material containing immobilized leukemia inhibitory factor (LIF). To immobilize LIF, we synthesized photoreactive gelatin mixed with LIF and cast the mixture on a polystyrene plate, which was then dried. LIF was immobilized by photoirradiation in the presence or absence of a photo mask. The plate was washed until LIF was no

Hiroshi Makino; Hirokazu Hasuda; Yoshihiro Ito

2004-01-01

346

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

347

Researchers Find Abnormal Cells in the Blood Years before Leukemia is Diagnosed  

Cancer.gov

Researchers have shown that abnormal white blood cells can be present in patients' blood more than six years prior to the diagnosis of a chronic form of lymphocytic leukemia. This finding may lead to a better understanding of the cellular changes that characterize the earliest stages of the disease and how it progresses.

348

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

349

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

ClinicalTrials.gov

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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 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); Recurrent Adult Acute Myeloid Leukemia

2014-07-02

350

The Multiple Mechanisms of Cell Death Triggered by Resveratrol in Lymphoma and Leukemia  

PubMed Central

Lymphoma and leukemia represent a serious threat to human health and life expectancy. Resveratrol is, among the natural-derived chemopreventive molecules, one of the most effective and better studied. In this paper the main mechanisms of cell death triggered by- or linked to- resveratrol are reviewed and discussed. The main focus is on lymphoma and leukemia experimental models where resveratrol has been tested and investigated at the cellular, molecular or physiological levels. The most relevant in vivo challenges involving resveratrol are also reported and analyzed in order to define the key features of this polyphenol and the potential for the treatment of hematologic tumors. PMID:24658441

Frazzi, Raffaele; Tigano, Marco

2014-01-01

351

Current status of hematopoietic stem cell transplant in chronic myeloid leukemia  

PubMed Central

Indications for hematopoietic stem cell transplant (HSCT) in chronic myeloid leukemia (CML) have changed over time. This change has largely been influenced by the advent of tyrosine kinase inhibitors, increased understanding of the mechanisms underlying disease phase progression as well as drug resistance, refinement of transplant techniques and exploitation of graft versus leukemia effect in this disease. Here, we have discussed the status of HSCT in CML in the present era with regards to the current indications, factors determining outcome and management strategies for posttransplant relapse.

Gupta, Alok; Khattry, Navin

2014-01-01

352

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

353

CRIF1 Interacting with CDK2 Regulates Bone Marrow Microenvironment-Induced G0/G1 Arrest of Leukemia Cells  

PubMed Central

Background To assess the level of CR6-interacting factor 1 (CRIF1), a cell cycle negative regulator, in patients with leukemia and investigate the role of CRIF1 in regulating leukemia cell cycle. Methods We compared the CRIF1 level in bone marrow (BM) samples from healthy and acute myeloid leukemia (AML), iron deficiency anemia (IDA) and AML-complete remission (AML-CR) subjects. We also manipulated CRIF1 level in the Jurkat cells using lentivirus-mediated overexpression or siRNA-mediated depletion. Co-culture with the BM stromal cells (BMSCs) was used to induce leukemia cell cycle arrest and mimic the BM microenvironment. Results We found significant decreases of CRIF1 mRNA and protein in the AML group. CRIF1 overexpression increased the proportion of Jurkat cells arrested in G0/G1, while depletion of endogenous CRIF1 decreased cell cycle arrest. Depletion of CRIF1 reversed BMSCs induced cell cycle arrest in leukemia cells. Co-immunoprecipitation showed a specific binding of CDK2 to CRIF1 in Jurkat cells during cell cycle arrest. Co-localization of two proteins in both nucleus and cytoplasm was also observed with immunofluorescent staining. Conclusion CRIF1 may play a regulatory role in the BM microenvironment-induced leukemia cell cycle arrest possibly through interacting with CDK2 and acting as a cyclin-dependent kinase inhibitor. PMID:24520316

Xiao, Yanni; Xiang, Lixing; Ye, Xingde; Deng, Xiaojun; Zhao, Jiang; Li, Zhongjun

2014-01-01

354

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

PubMed

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. PMID:24104188

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

2013-10-01

355

The plant alkaloid usambarensine intercalates into DNA and induces apoptosis in human HL60 leukemia cells.  

PubMed

Usambarensine is a plant alkaloid isolated from the roots of Strychnos usambarensis collected in Central Africa. This bis-indole compound displays potent antiamoebic activities and shows antigardial, antimalarial and cytotoxic effects. Usambarensine is highly toxic to B16 melanoma cells and inhibits the growth of leukemia and carcinoma cells. To date, the molecular basis for its diverse biological effects remains totally unknown. However, its capacity to inhibit nucleic acids synthesis in melanoma cells, on the one hand, and its structural analogy with DNA-binding pyridoindole plant alkaloids recently studied (cryptolepine and matadine), on the other hand, suggested that usambarensine could also bind to DNA. Consequently, we studied the strength and mode of binding to DNA of usambarensine by means of absorption, circular and linear dichroism. The results of the optical measurements indicate that the alkaloid effectively binds to DNA and behaves as a typical intercalating agent. Biochemical experiments indicated that, in contrast to cryptolepine and matadine, usambarensine does not interfere with the catalytic activity of topoisomerase II. Human HL60 leukemia cells were used to assess the cytotoxicity of the alkaloid and its effect on the cell cycle. Usambarensine treatment is associated with a loss of cells in the G1 phase accompanied with a large increase in the sub-G1 region which is characteristic of apoptotic cells. The DNA of usambarensine-treated cells was severely fragmented and the proteolytic activity of DEVD-caspases is enhanced. Usambarensine is thus characterized as DNA intercalator inducing apoptosis in leukemia cells. PMID:10697543

Dassonneville, L; Wattez, N; Mahieu, C; Colson, P; Houssier, C; Frederich, M; Tits, M; Angenot, L; Bailly, C

1999-01-01

356

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

357

[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

358

CD44 activation enhances acute monoblastic leukemia cell survival via Mcl-1 upregulation.  

PubMed

Survival of acute myeloid leukemia (AML) cells is regulated by their adherence to bone marrow stromal environment. Several adhesion molecules mediate interactions between AML cells and stroma, but their specific role in AML cell survival is still poorly understood. Here, we show that CD44 activation with the Hermes-3 monoclonal antibody enhances primary AML5 blast survival and increases apoptosis resistance of THP-1 monoblastic leukemia cells. Moreover, we show that CD44 activation upregulates the anti-apoptotic Mcl-1 protein and that Mcl-1 is essential for apoptosis resistance of THP-1 cells. These results suggest that Mcl-1 inhibitors might be required to block pro-survival activity of CD44 in AML5. PMID:21993315

Sansonetti, Arnaud; Bourcier, Sébastien; Durand, Laetitia; Chomienne, Christine; Smadja-Joffe, Florence; Robert-Lézénès, Jacqueline

2012-03-01

359

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

PubMed Central

The most common human leukemia is B cell chronic lymphocytic leukemia (CLL), a malignancy 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 the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression “signature,” irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin. Nonetheless, the expression of hundreds of other genes correlated with the Ig mutational status, including many genes that are modulated in expression during mitogenic B cell receptor signaling. These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease. PMID:11733578

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

2001-01-01

360

SPARC promotes leukemic cell growth and predicts acute myeloid leukemia outcome  

PubMed Central

Aberrant expression of the secreted protein, acidic, cysteine-rich (osteonectin) (SPARC) gene, which encodes a matricellular protein that participates in normal tissue remodeling, is associated with a variety of diseases including cancer, but the contribution of SPARC to malignant growth remains controversial. We previously reported that SPARC was among the most upregulated genes in cytogenetically normal acute myeloid leukemia (CN-AML) patients with gene-expression profiles predictive of unfavorable outcome, such as mutations in isocitrate dehydrogenase 2 (IDH2-R172) and overexpression of the oncogenes brain and acute leukemia, cytoplasmic (BAALC) and v-ets erythroblastosis virus E26 oncogene homolog (ERG). In contrast, SPARC was downregulated in CN-AML patients harboring mutations in nucleophosmin (NPM1) that are associated with favorable prognosis. Based on these observations, we hypothesized that SPARC expression is clinically relevant in AML. Here, we found that SPARC overexpression is associated with adverse outcome in CN-AML patients and promotes aggressive leukemia growth in murine models of AML. In leukemia cells, SPARC expression was mediated by the SP1/NF-?B transactivation complex. Furthermore, secreted SPARC activated the integrin-linked kinase/AKT (ILK/AKT) pathway, likely via integrin interaction, and subsequent ?-catenin signaling, which is involved in leukemia cell self-renewal. Pharmacologic inhibition of the SP1/NF-?B complex resulted in SPARC downregulation and leukemia growth inhibition. Together, our data indicate that evaluation of SPARC expression has prognosticative value and SPARC is a potential therapeutic target for AML. PMID:24590286

Alachkar, Houda; Santhanam, Ramasamy; Maharry, Kati; Metzeler, Klaus H.; Huang, Xiaomeng; Kohlschmidt, Jessica; Mendler, Jason H.; Benito, Juliana M.; Hickey, Christopher; Neviani, Paolo; Dorrance, Adrienne M.; Anghelina, Mirela; Khalife, Jihane; Tarighat, Somayeh S.; Volinia, Stefano; Whitman, Susan P.; Paschka, Peter; Hoellerbauer, Pia; Wu, Yue-Zhong; Han, Lina; Bolon, Brad N.; Blum, William; Mrozek, Krzysztof; Carroll, Andrew J.; Perrotti, Danilo; Andreeff, Michael; Caligiuri, Michael A.; Konopleva, Marina; Garzon, Ramiro; Bloomfield, Clara D.; Marcucci, Guido

2014-01-01

361

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; Foa, Robin

2014-01-01

362

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

363

Restoration of natural killer cell cytotoxicity by VEGFR-3 inhibition in myelogenous leukemia.  

PubMed

Acute myeloid leukemia (AML) cells in vivo are constantly exposed to lymphangiogenic cytokines such as VEGF-C. However, it is poorly understood how the VEGF-C signaling modulates the immune functions in the tumor microenvironment. We have previously reported that natural killer (NK) cells in AML patients strongly upregulated VEGFR-3, the major VEGF-C receptor, and that the VEGFR-3 expression level in NK cells inversely correlates with their cytotoxic potential. These findings have led us to hypothesize that VEGFR-3 inhibition may reinstate the cytotoxic capacity of the AML-associated NK cells. To address this hypothesis, we employed a pharmaceutical approach to block the VEGFR-3 function in the murine model of syngeneic myelogenous leukemia. Using various molecular and cellular analyses, we assessed the correlation between VEGFR-3 inhibition and NK cell cytotoxicity. Indeed, we found that leukemic environment is highly enriched with lymphangiogenic stimuli, and that VEGFR-3 inhibition restored NK cell killing function with an increased IFN-? level, providing a therapeutic implication of VEGFR-3 against AML. Together, we demonstrate the therapeutic value of functional modulation of NK cells by blocking VEGFR-3, and provide a possibility of advanced therapeutic approaches using immune cells against myelogenous leukemia. PMID:25157650

Lee, Ji Yoon; Park, Sohye; Min, Woo-Sung; Kim, Hee-Je

2014-11-28

364

In vitro and in vivo Study of Cell Growth Inhibition of Simvastatin on Chronic Myelogenous Leukemia Cells  

Microsoft Academic Search

Background: Statins, a family of 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase inhibitors, are being investigated for the therapy and prevention of cancers. Here we aimed to investigate the effects of simvastatin on chronic myelogenous leukemia (CML) cells in vitro and in vivo, and to elucidate the mechanisms. Methods: Cell proliferation and cell cycle were measured after K562 cells were incubated with

Yong-Chang Yang; Wen-Fang Huang; Liang-Min Chuan; Dai-Wen Xiao; Ya-Li Zeng; Ding-An Zhou; Guo-Qiang Xu; Wen Liu; Bo Huang; Qi Hu

2008-01-01

365

Evaluation of dendritic cells loaded with apoptotic cancer cells or expressing tumour mRNA as potential cancer vaccines against leukemia  

Microsoft Academic Search

BACKGROUND: Leukemia is a clonal disorder characterized by uncontrolled proliferation of haematopoietic cells, and represents the most common form of cancer in children. Advances in therapy for childhood leukemia have relied increasingly on the use of high-dose chemotherapy often combined with stem-cell transplantation. Despite a high success rate and intensification of therapy, children still suffer from relapse and progressive disease

Silvija Jarnjak-Jankovic; Rolf D Pettersen; Stein Sæbøe-Larssen; Finn Wesenberg; Gustav Gaudernack

2005-01-01

366

Investigation of inducing effect of specific cytotoxicity of CTLS by antigen peptides from T lymphocytic leukemia cells  

Microsoft Academic Search

Objective: To investigate the characteristics of specific antitumor immunity induced by antigen peptides mixture from T lymphocytic\\u000a leukemia cells. Method: Antigen peptides mixtures were prepared from different leukemia cell lines and then bound with Hsp70in vitro. Human peripheral blood mononuclear cells (PBMC) were culturedin vitro, and activated with Hsp70-antigen peptides. The activated PBMC was cultured continuouslyin vitro, and used as

Gui-mei Zhang; Bo Huang; Dong Li; Hong-tao Wang; Zuo-hua Feng

2003-01-01

367

HTLV-V: A New Human Retrovirus Isolated in a Tac-Negative T Cell Lymphoma\\/Leukemia  

Microsoft Academic Search

A new human retrovirus was isolated from a continuous cell line derived from a patient with CD4+ Tac- cutaneous T cell lymphoma\\/leukemia. This virus is related to but distinct from human T cell leukemia\\/lymphoma virus types I and II (HTLV-I and HTLV-II) and human immunodeficiency virus (HIV-1). With the use of a fragment of provirus cloned from one patient with

Vittorio Manzari; Angela Gismondi; Giovanni Barillari; Stefania Morrone; Andrea Modesti; Loredana Albonici; Laura de Marchis; Vito Fazio; Angela Gradilone; Massimo Zani; Luigi Frati; Angela Santoni

1987-01-01

368

Wnt pathway contributes to the protection by bone marrow stromal cells of acute lymphoblastic leukemia cells and is a potential therapeutic target  

PubMed Central

Leukemia cells are protected by various components of its microenvironment, including marrow stromal cells (MSCs). To understand the molecular mechanisms underlying this protection, we cultured acute lymphoblastic leukemia (ALL) cells with MSCs and studied the effect of the latter on the molecular profiling of ALL cells at the mRNA and protein levels. Our results indicated that activated Wnt signaling in ALL cells is involved in MSC-mediated drug resistance. Blocking the Wnt pathway sensitized the leukemia cells to chemotherapy and improved overall survival in a mouse model. Targeting the Wnt pathway may be an innovative approach to the treatment of ALL. PMID:23333798

Yang, Yang; Mallampati, Saradhi; Sun, Baohua; Zhang, Jing; Kim, Sangbae; Lee, Ju-Seog; Gong, Yun; Cai, Zhen; Sun, Xiaoping

2013-01-01

369

Deregulation of Mitochondrial ATPsyn-? in Acute Myeloid Leukemia Cells and with Increased Drug Resistance  

PubMed Central

The mechanisms underlying the development of multidrug resistance in acute myeloid leukemia are not fully understood. Here we analyzed the expressions of mitochondrial ATPsyn-? in adriamycin-resistant cell line HL-60/ADM and its parental cell line HL-60. Meanwhile we compared the differences of mitochondrial ATPsyn-? expression and ATP synthase activity in 110 acute myeloid leukemia (AML, non-M3) patients between relapsed/refractory and those in remission. Our results showed that down-regulation of ATPsyn-? expression by siRNA in HL-60 cells increased cell viability and apoptotic resistance to adriamycin, while up-regulation of mitochondrial ATPsyn-? in HL-60/ADM cells enhanced cell sensitivity to adriamycin and promoted apoptosis. Mitochondrial ATPsyn-? expression and ATP synthase activity in relapsed/refractory acute myeloid leukemia patients were downregulated. This downregulated ATPsyn-? expression exhibited a positive correlation with the response to adriamycin of primary cells. A lower expression of ATPsyn-? in newly diagnosed or relapsed/refractory patients was associated with a shorter first remission duration or overall survival. Our findings show mitochondrial ATPsyn-? plays an important role in the mechanism of multidrug resistance in AML thus may present both a new marker for prognosis assessment and a new target for reversing drug resistance. PMID:24391795

Li, Ruijuan; Liu, Sufang; Xu, Yunxiao; Zheng, Wenli; Yi, Yan; Luo, Yunya; Gong, Fanjie; Peng, Honglin; Pei, Minfei; Deng, Mingyang; Zhang, Guangsen

2013-01-01

370

Cytotoxic effect of trans-cinnamaldehyde on human leukemia K562 cells  

PubMed Central

Aim: To investigate the effects of trans-cinnamaldehyde (TCA) on the human leukemia K562 cell line and the cytotoxicity of cytokine-induced killer (CIK) cells against K562 cells. Methods: Apoptosis, Fas expression, and mitochondrial transmembrane potential in K652 cells were analyzed using flow cytometry. K562 cells were labeled with CFSE. The cytotoxic effect of expanded CIK cells on CFSE-labeled K562 cells was determined by FACS flow cytometry. Results: Treatment with TCA 180 ?mol/L for 9 h induced apoptosis in 8.9%±1.23% of K562 cells. Treatment with 120 or 180 ?mol/L TCA for 24 h significantly increased the apoptotic cells to 18.63%±1.42 % and 38.98%±2.74%, respectively. TCA significantly upregulates Fas expression and decreases mitochondrial transmembrane potential in K562 cells. TCA treatment at 120 and 180 ?mol/L for 9 h enhanced the percentage of lysis of K562 cells by expanded CIK cells from 34.84%±2.13% to 48.21%±2.22 % and 64.81%±3.22% at the E:F ratio of 25:1 and from 49.26%±3.22% to 57.81%±5.13% and 73.36%±5.98% at E:F ratio of 50:1. Conclusion: TCA exerts cytotoxic effects on human leukemia K562 cells by inducing apoptosis and synergizing the cytotoxicity of CIK cells against K562 cells. These properties of TCA are beneficial to the treatment of leukemia, even in the patients who have received hematopoietic stem cells transplantation (HSCT). PMID:20581850

Zhang, Jia-hua; Liu, Li-qiong; He, Yan-li; Kong, Wei-jia; Huang, Shi-ang

2010-01-01

371

Autologous and allogeneic stem cell transplantations for poor-risk chronic lymphocytic leukemia  

Microsoft Academic Search

We report here on the long-term follow-up on 162 patients with high-risk chronic lymphocytic leukemia (CLL) who have undergone hematopoietic stem cell trans- plantation (SCT) at a single center from 1989 to 1999. Twenty-five patients with human leukocyte antigen (HLA)-matched sibling donors underwent T-cell-depleted allogeneic SCT, and 137 patients without HLA-matched sibling donors underwent autologous SCT. The 100-day mortality was

John G. Gribben; David Zahrieh; Katherine Stephans; Lini Bartlett-Pandite; Edwin P. Alyea; David C. Fisher; Arnold S. Freedman; Peter Mauch; Robert Schlossman; Lecia V. Sequist; Robert J. Soiffer; Blossom Marshall; Donna Neuberg; Jerome Ritz; Lee M. Nadler

2005-01-01

372

Allogeneic Hematopoietic Stem Cell Transplantation in Adult Acute Lymphocytic Leukemia: Impact of Donor Source on Survival  

Microsoft Academic Search

We studied the relative impact of donor source on outcomes following myeloablative hematopoietic stem cell transplantation (HSCT) for adult patients with acute lymphocytic leukemia (ALL). In this single center study, 138 patients aged 18-61 (median 31) years underwent myeloablative conditioning followed by allogeneic HSCT. Stem cell source was an HLA matched related donor (MRD) in 90, HLA matched unrelated donor (URD:M)

Priya Kumar; Todd E. Defor; Claudio Brunstein; Juliet N. Barker; John E. Wagner; Daniel J. Weisdorf; Linda J. Burns

2008-01-01

373

Apparent expansion of CD34+ cells during the evolution of myelodysplastic syndromes to acute myeloid leukemia  

Microsoft Academic Search

Myelodysplastic syndromes (MDS) are highly proliferative bone marrow (BM) disorders where the primary lesion presumably affects a CD34+ early progenitor or stem cell. We investigated the proliferative characteristics of CD34+ cells of 33 untreated MDS patients (19 RA, 5 RARS, 7 RAEB, 2 RAEBt) and five patients with acute myeloid leukemia after MDS (sAML). All patients received a 1-h infusion

LFR Span; SE Dar; V Shetty; SD Mundle; L Broady-Robinson; S Alvi; RAP Raymakers; T de Witte; A Raza

1998-01-01

374

Aggressive Variant of Morphologically Typical T Large Granular Lymphocyte Leukemia\\/Lymphoma Lacking NK Cell Markers  

Microsoft Academic Search

A 46-year-old woman with a previous diagnosis of sarcoidosis presented with morphologically typical large granular lymphocyte (LGL) leukemia\\/lymphoma with an aggressive clinical course. Epstein-Barr virus DNA was detected in peripheral blood mononuclear cells by PCR. The phenotype was typical of the T cell lineage (CD2+ CD3+ CD5+ CD7+ CD8+ TCR??+) but with the absence of the CD16, CD56, CD57 NK

Roberto Passetto Falcão; Belinda Pinto Simões; Aglair B. Garcia; Benedito A. F. Fonseca; João Terra Filho

2000-01-01

375

Quantitative molecular monitoring of residual tumor cells in chronic lymphocytic leukemia  

Microsoft Academic Search

. New therapeutic approaches for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) can induce remarkable responses. Molecular remissions have been observed occasionally after high-dose chemotherapy. Thus, new improved techniques to monitor residual tumor cells on a molecular basis in CLL are warranted. For this purpose, a real-time quantitative allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) for patients with B-CLL was

T. Pfitzner; M. Reiser; S. Barth; P. Borchmann; H. Schulz; T. Schinköthe; F. Oberhäuser; J. Wessels; M. Tur; V. Diehl; A. Engert

2002-01-01

376

Immunotoxin-mediated Inhibition of Chronic Lymphocytic Leukemia Cell Proliferation in Humans1  

Microsoft Academic Search

We evaluated the cytotoxicity of the immunotoxin OKT1-SAP on fresh B-chronic lymphocytic leukemia (B-CLL) cells from 31 consecutive patients. OKT1-SAP comprised the OKT1 (CDS) monoclonal antibody disilludi' linked to saporin-6 (SAP) ribosome-inactivating protein from the plant Saponaria officinali!. The effect of OKT1-SAP on target CD5- positive B-CLL cells was estimated using an in vitro proliferation inhi bition assay in which

Salvatore Siena; Marco Bregni; Anna Formosa; Bruno Brando; Paola Marenco; Douglas A. Lappi; Gianni Bonadonna; A. Massimo Gianni

377

Treatment-related mortality and graft-versus-leukemia activity after allogeneic stem cell transplantation for chronic lymphocytic leukemia using intensity-reduced conditioning  

Microsoft Academic Search

Allogeneic stem cell transplantation (SCT) using reduced-intensity conditioning (RIC) has potential to be a promising treatment of aggressive chronic lymphocytic leukemia (CLL). Since available clinical data obtained with this novel approach are very limited, we have performed a survey on this issue. Data of 77 patients were collected from 29 European Group for Blood and Marrow Transplantation centers. Median age

P Dreger; R Brand; J Hansz; D Milligan; P Corradini; J Finke; G L Deliliers; R Martino; N Russell; A van Biezen; M Michallet; D Niederwieser

2003-01-01

378

Antibody-dependent cell-mediated cytotoxicity overcomes NK cell-resistance in MLL-rearranged leukemia expressing inhibitory KIR ligands but not activating ligands  

PubMed Central

Purpose Leukemias with MLL gene rearrangement are associated with a poor prognosis. Natural killer (NK) cell therapy is a potential treatment, but leukemia cells may be resistant. Here, we sought to determine the susceptibility of MLL-rearranged leukemia cells to NK cell lysis and to develop a novel immunotherapeutic approach to optimize NK cell therapy, including the use of an antibody against leukemia-associated antigen and the elimination of killer-cell immunoglobulin-like receptor (KIR)–mediated inhibition. Experimental Design Three MLL-rearranged leukemia cell lines (RS4;11, SEM, and MV4-11) and primary leukemia blasts were assessed for surface phenotype and susceptibility to NK cell lysis with or without antibodies against CD19 (XmAb5574), CD33 (lintuzumab), or KIR ligands. Results All three cell lines were resistant to NK cell lysis, had some inhibitory KIR ligands and protease inhibitor-9, and expressed low levels of NKG2D activating ligands and adhesion molecules. After treatment with XmAb5574 or lintuzumab, MLL-rearranged leukemia cells were efficiently killed by NK cells. The addition of pan–major histocompatibility complex class I antibody, which blocked inhibitory KIR-HLA interaction, further augmented degranulation in all three KIR2DL1, KIR2DL2/3, and KIR3DL1 subsets of NK cells based on the rule of missing-self recognition. A mouse model showed a decreased rate of leukemia progression in vivo as monitored by bioluminescence imaging and longer survival after antibody treatment. Conclusion Our data support the use of a triple immunotherapy approach, including an antibody directed against tumor-associated antigen, KIR-mismatched NK cell transplantation, and inhibitory KIR blockade, for the treatment of NK cell–resistant MLL-rearranged leukemias. PMID:23014531

Chan, Wing Keung; Sutherland, May Kung; Li, Ying; Zalevsky, Jonathan; Schell, Sarah; Leung, Wing

2012-01-01

379

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

380

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

381

Adipose tissue attracts and protects acute lymphoblastic leukemia cells from chemotherapy.  

PubMed

Obesity is associated with an increased risk of acute lymphoblastic leukemia (ALL) relapse. Using mouse and cell co-culture models, we investigated whether adipose tissue attracts ALL to a protective microenvironment. Syngeneically implanted ALL cells migrated into adipose tissue within ten days. In vitro, murine ALL cells migrated towards adipose tissue explants and 3T3-L1 adipocytes. Human and mouse ALL cells migrated toward adipocyte conditioned media, which was mediated by SDF-1?. In addition, adipose tissue explants protected ALL cells against daunorubicin and vincristine. Our findings suggest that ALL migration into adipose tissue could contribute to drug resistance and potentially relapse. PMID:23332453

Pramanik, Rocky; Sheng, Xia; Ichihara, Brian; Heisterkamp, Nora; Mittelman, Steven D

2013-05-01

382

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

2014-07-22

383

Differential gene expression profiles of human leukemia cell lines exposed to benzene and its metabolites.  

PubMed

Benzene is a well-known environmental pollutant that can induce hematotoxicity, aplastic anemia, acute myelogenous leukemia, and lymphoma. Benzene toxicity is likely mediated through metabolites induced by means of multiple pathways. Although benzene metabolites are known to induce oxidative stress and disrupt the cell cycle, the mechanism underlying leukemogenesis is not fully understood. The aim of this study was to analyze the genome-wide expression profiles of human promyelocytic leukemia HL-60 cells that had been exposed to benzene and its metabolites. This was carried out using whole human genome oligonucleotide microarrays to ascertain potential biomarkers. Genes that were differentially expressed (>1.5-fold and p-values <0.05) after exposure to benzene (BZ), hydroquinone (HQ), and 1,4-benzoquinone (BQ) were then classified with GO, KEGG and GSEA pathway annotation. All genes that were identified were then functionally categorized as being involved in the cell cycle, the p53 signaling pathway, apoptosis, the MAPK signaling pathway, or the T cell receptor signaling pathway. Functionally important genes were further validated by means of real-time RT-PCR. The results showed that EGR1, PMAIP1, AR, CCL2, CD69, HSPA8, SLC7A11, HERPUD1, ELK1, and MKI57 genes altered their expression profiles. Similar expression profiles were also found in human erythromyeloblastoid leukemia K562 cells and in human leukemic monocyte lymphoma U937 cells. In conclusion, gene expression profiles along with GO, KEGG and GSEA pathway annotation analysis have provided an insight into the leukemogenesis as well as highlighted potential gene-based biomarkers of human leukemia cell lines when they are exposed to benzene and its metabolites. PMID:21843810

Sarma, Sailendra Nath; Kim, Youn-Jung; Ryu, Jae-Chun

2011-09-01

384

Veliparib and Temozolomide in Treating Patients With Acute Leukemia  

ClinicalTrials.gov

Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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); B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

2014-10-03

385

Adult T-cell leukemia-lymphoma associated with follicular mucinosis.  

PubMed

: Follicular mucinosis is frequently associated with follicular mycosis fungoides, but its association with adult T-cell leukemia-lymphoma (ATLL) is extremely rare. We report a case of a 50-year-old female patient with a history of ATLL, after multiple treatments, with residual/recurrent skin tumors in the forehead and legs. Biopsy of a skin tumor from the forehead revealed a perifollicular and intrafollicular atypical lymphoid infiltrate with abundant mucin deposition. Immunohistochemical stains showed that the atypical cells were positive for CD3, CD4, and CD25. Reverse transcription polymerase chain reaction performed on the tissue sections confirmed the presence of human T-cell leukemia virus in the biopsies of skin tumors. To our knowledge, this is only the third reported case of a follicular mucinosis in the setting of ATLL. PMID:24614206

Ballester, Leomar Y; Cowen, Edward W; Richard Lee, Chyi-Chia

2014-11-01

386

Induction of multiple independent T-cell lymphomas in rats inoculated with MOloney murine leukemia virus.  

PubMed Central

Tumor cell DNA derived from different lymphoid organs of 30 rats serially inoculated at birth with Moloney murine leukemia virus (MoMuLV) was examined by Southern blot analysis and hybridization to the following DNA probes: MoMuLV long terminal repeat (LTR), Moloney leukemia virus integration regions 1, 2, 3, and 4 (Mlvi-1, Mlvi-2, Mlvi-3, and Mlvi-4), T-cell receptor beta locus, and immunoglobulin heavy chain locus. This analysis revealed that the tumors segregating in different lymphoid organs in 10% of the animals were clonally unrelated. These findings are consistent with the hypothesis that the MoMuLV-induced rat thymic lymphomas are polyclonal in origin. At least two factors may be responsible for this phenomenon: (i) increase in the number of the available target cells in virus-infected animals, and (ii) genetic instability associated with provirus integration in the developing premalignant clones. Images PMID:2786211

Bellacosa, A; Lazo, P A; Bear, S E; Shinton, S; Tsichlis, P N

1989-01-01

387

Variant Human T-cell Lymphotropic Virus Type 1c and Adult T-cell Leukemia, Australia  

PubMed Central

Human T-cell lymphotropic virus type 1 is endemic to central Australia among Indigenous Australians. However, virologic and clinical aspects of infection remain poorly understood. No attempt has been made to control transmission to indigenous children. We report 3 fatal cases of adult T-cell leukemia/lymphoma caused by human T-cell lymphotropic virus type 1 Australo-Melanesian subtype c. PMID:24047544

Cassar, Olivier; Bardy, Peter; Kearney, Daniel; Gessain, Antoine

2013-01-01

388

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

389

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

390

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.

391

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

392

The alkaloid emetine as a promising agent for the induction and enhancement of drug-induced apoptosis in leukemia cells.  

PubMed

Emetine, a natural alkaloid from Psychotria ipecacuanha, has been used in phytomedicine to induce vomiting, and to treat cough and severe amoebiasis. Certain data suggest the induction of apoptosis by emetine in leukemia cells. Therefore, we examined the suitability of emetine for the sensitisation of leukemia cells to apoptosis induced by cisplatin. In response to emetine, we found a strong reduction in viability, an induction of apoptosis and caspase activity comparable to the cytotoxic effect of cisplatin. Moreover, emetine had an additive effect and increased cisplatin-induced apoptosis. Mechanistically, we demonstrate by DNA array analysis that emetine alone or together with cisplatin down-regulates several anti-survival genes and up-regulates several pro-apoptotic signalling molecules along with other effects on signalling. These data show that emetine is a strong inducer of apoptosis in leukemia cells and could be a suitable cytotoxic drug alone or in combination with other chemotherapeutics to sensitise leukemia cells to apoptosis. PMID:17671728

Möller, Maren; Herzer, Kerstin; Wenger, Till; Herr, Ingrid; Wink, Michael

2007-09-01

393

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.

394

Polyphenols are responsible for the proapoptotic properties of pomegranate juice on leukemia cell lines  

PubMed Central

Pomegranates have shown great promise as anti-cancer agents in a number of cancers including clinical trials in prostate cancer. We have previously shown pomegranate juice (PGJ) induced apoptosis and preferentially alters the cell cycle in leukemia cell lines compared with nontumor control cells. However, the agents responsible have not yet been fully elucidated. Treatment of four leukemia cell lines with five fractions obtained from PGJ by solid phase extraction demonstrated that only the acetonitrile fractions decreased adenosine triphosphate (ATP) levels in all leukemia cell lines. Acetonitrile fractions also significantly activated caspase-3 and induced nuclear morphology characteristic of apoptosis. S phase arrest was induced by acetonitrile fractions which matched S phase arrest seen previously following whole PGJ treatments. The acetonitrile fractions contained higher phenol content than whole PGJ whereas only low levels of phenols were seen in any other fraction. Liquid chromatography mass spectrometry (LC–MS) analysis demonstrated that acetonitrile fractions were enriched in ellagitannins, ellagic acid, and hydroxycinnamic acid derivatives but depleted in anthocyanins. Individual treatments with identified compounds demonstrated that the ellagitannin: punicalagin was the most active and mimicked the responses seen following acetonitrile fraction treatment. Bioactive components within pomegranate were confined to the acetonitrile fraction of PGJ. The enrichment in ellagitannins and hydroxycinnamic acids suggest these may provide the majority of the bioactivities of PGJ. Individual treatments with compounds identified demonstrated that the ellagitannin: punicalagin was the most active agent, highlighting this compound as a key bioactive agent in PGJ. PMID:24804028

Dahlawi, Haytham; Jordan-Mahy, Nicola; Clench, Malcolm; McDougall, Gordon J; Maitre, Christine Lyn

2013-01-01

395

Selective BCL-2 Inhibition by ABT-199 Causes On Target Cell Death in Acute Myeloid Leukemia  

PubMed Central

B-cell leukemia/lymphoma 2 (BCL-2) prevents commitment to programmed cell death at the mitochondrion. It remains a challenge to identify those tumors that are best treated by inhibition of BCL-2. Here we demonstrate that acute myeloid leukemia (AML) cell lines, primary patient samples, and murine primary xenografts are very sensitive to treatment with the selective BCL-2 antagonist ABT-199. In primary patient cells, the median IC50 was approximately 10 nM, and cell death occurred within 2 h. Our ex vivo sensitivity results compare favorably with those observed for chronic lymphocytic leukemia (CLL), a disease for which ABT-199 has demonstrated consistent activity in clinical trials. Moreover, mitochondrial studies using BH3 profiling demonstrate activity at the mitochondrion that correlates well with cytotoxicity, supporting an on target mitochondrial mechanism of action. Our protein and BH3 profiling studies provide promising tools that can be tested as predictive biomarkers in any clinical trial of ABT-199 in AML. PMID:24346116

Pan, Rongqing; Hogdal, Leah J.; Benito, Juliana M; Bucci, Donna; Han, Lina; Borthakur, Gautam; Cortes, Jorge; DeAngelo, Daniel J.; Debose, LaKeisha; Mu, Hong; Dohner, Hartmut; Gaidzik, Verena I.; Galinsky, Ilene; Golfman, Leonard S.; Haferlach, Torsten; Harutyunyan, Karine G.; Hu, Jianhua; Leverson, Joel D; Marcucci, Guido; Muschen, Markus; Newman, Rachel; Park, Eugene; Ruvolo, Peter P.; Ruvolo, Vivian; Ryan, Jeremy; Schindela, Sonja; Zweidler-McKay, Patrick; Stone, Richard M.; Kantarjian, Hagop; Andreeff, Michael; Konopleva, Marina; Letai, Anthony G.

2014-01-01

396

Niche-based screening identifies small-molecule inhibitors of leukemia stem cells  

PubMed Central

Efforts to develop more effective therapies for acute leukemia may benefit from high-throughput screening systems that reflect the complex physiology of the disease, including leukemia stem cells (LSCs) and supportive interactions with the bone-marrow microenvironment. The therapeutic targeting of LSCs is challenging because LSCs are highly similar to normal hematopoietic stem and progenitor cells (HSPCs) and are protected by stromal cells in vivo. We screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function. Among those that inhibited malignant cells but spared HSPCs was the cholesterol-lowering drug lovastatin. Lovastatin showed anti-LSC activity in vitro and in an in vivo bone marrow transplantation model. Mechanistic studies demonstrated that the effect was on-target, via inhibition of HMGCoA reductase. These results illustrate the power of merging physiologically-relevant models with high-throughput screening. PMID:24161946

Mukherjee, Siddhartha; Kahn, Alissa R; Stewart, Alison L; Logan, David J; Negri, Joseph M; Duvet, Mildred; Jaras, Marcus; Puram, Rishi; Dancik, Vlado; Al-Shahrour, Fatima; Kindler, Thomas; Tothova, Zuzana; Chattopadhyay, Shrikanta; Hasaka, Thomas; Narayan, Rajiv; Dai, Mingji; Huang, Christina; Shterental, Sebastian; Chu, Lisa P; Haydu, J Erika; Shieh, Jae Hung; Steensma, David P; Munoz, Benito; Bittker, Joshua A; Shamji, Alykhan F; Clemons, Paul A; Tolliday, Nicola J; Carpenter, Anne E; Gilliland, D Gary; Stern, Andrew M; Moore, Malcolm A S; Scadden, David T; Schreiber, Stuart L; Ebert, Benjamin L; Golub, Todd R

2014-01-01

397

Targeting the leukemic stem cell: the Holy Grail of leukemia therapy  

PubMed Central

Since the discovery of leukemic stem cells (LSCs) over a decade ago, many of their critical biological properties have been elucidated, including their distinct replicative properties, cell surface phenotypes, their increased resistance to chemo-therapeutic drugs and the involvement of growth-promoting chromosomal translocations. Of particular importance is their ability to transfer malignancy to non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. Furthermore, numerous studies demonstrate that acute myeloid leukemia arises from mutations at the level of stem cell, and chronic myeloid leukemia is also a stem cell disease. In this review, we will evaluate the main characteristics of LSCs elucidated in several well-documented leukemias. In addition, we will discuss points of therapeutic intervention. Promising therapeutic approaches include the targeting of key signal transduction pathways (for example, PI3K, Rac and Wnt) with small-molecule inhibitors and specific cell surface molecules (for example, CD33, CD44 and CD123), with effective cytotoxic antibodies. Also, statins, which are already widely therapeutically used for a variety of diseases, show potential in targeting LSCs. In addition, drugs that inhibit ATP-binding cassette transporter proteins are being extensively studied, as they are important in drug resistance—a frequent characteristic of LSCs. Although the specific targeting of LSCs is a relatively new field, it is a highly promising battleground that may reveal the Holy Grail of cancer therapy. PMID:18800146

Misaghian, N; Ligresti, G; Steelman, LS; Bertrand, FE; Basecke, J; Libra, M; Nicoletti, F; Stivala, F; Milella, M; Tafuri, A; Cervello, M; Martelli, AM

2008-01-01

398

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 role of NK cells has been clearly demonstrated in the therapy of high risk leukemias in the haploidentical hematopoietic stem cell (HSC) transplantation setting. NK cells derived from donor HSC kill leukemic cells residual after the conditioning regimen, thus preventing leukemia relapses. In addition, they also kill residual dendritic cells and T lymphocytes, thus preventing both GvH disease and graft rejection. PMID:24639677

Moretta, Lorenzo; Pietra, Gabriella; Montaldo, Elisa; Vacca, Paola; Pende, Daniela; Falco, Michela; Del Zotto, Genny; Locatelli, Franco; Moretta, Alessandro; Mingari, Maria Cristina

2014-01-01

399

Aberrant expression of the transcription factor Twist in adult T-cell leukemia.  

PubMed

Adult T-cell leukemia (ATL) is a T-cell malignancy etiologically associated with human T-cell leukemia virus type 1 (HTLV-1). Twist, a highly conserved basic helix-loop-helix transcription factor, is a newly identified oncogene. However, there are no reports on Twist expression in ATL. To define the role of Twist in leukemogenesis of ATL, we examined its expression in T-cell lines and PBMC. HTLV-1-infected T-cell lines and ATL cells expressed high levels of Twist compared with uninfected T-cell lines and normal PBMC. Immunohistochemistry showed immunostaining for Twist in ATL cells in ATL lymph nodes and skin lesions. Infection of normal PBMC with HTLV-1 induced Twist expression. Induction of the viral protein Tax in a human T-cell line led to upregulation of Twist. Tax-induced Twist expression involved the NF-kappaB and CREB signaling pathways. Twist augmented Tax-mediated HTLV-1 LTR and NF-kappaB activation. Short interfering RNA against Twist inhibited cell growth of HTLV-1-infected T-cell lines and downregulation of Twist expression in an HTLV-1-infected T-cell line inhibited the expression of Akt1, interleukin-2 receptor alpha chain, and Tax as well as the known target genes of Twist, YB-1 and Akt2. In conclusion, the results suggest that Tax-induced induction of Twist contributes to leukemogenesis of ATL. PMID:20071663

Tanji, Hiroe; Ishikawa, Chie; Sawada, Shigeki; Nakachi, Sawako; Takamatsu, Reika; Matsuda, Takehiro; Okudaira, Taeko; Uchihara, Jun-Nosuke; Ohshiro, Kazuiku; Tanaka, Yuetsu; Senba, Masachika; Uezato, Hiroshi; Ohshima, Koichi; Duc Dodon, Madeleine; Wu, Kou-Juey; Mori, Naoki

2010-01-13

400

Human NK Cells: From Surface Receptors to the Therapy of Leukemias and Solid Tumors  

PubMed Central

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 role of NK cells has been clearly demonstrated in the therapy of high risk leukemias in the haploidentical hematopoietic stem cell (HSC) transplantation setting. NK cells derived from donor HSC kill leukemic cells residual after the conditioning regimen, thus preventing leukemia relapses. In addition, they also kill residual dendritic cells and T lymphocytes, thus preventing both GvH disease and graft rejection. PMID:24639677

Moretta, Lorenzo; Pietra, Gabriella; Montaldo, Elisa; Vacca, Paola; Pende, Daniela; Falco, Michela; Del Zotto, Genny; Locatelli, Franco; Moretta, Alessandro; Mingari, Maria Cristina

2014-01-01