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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  

Microsoft Academic Search

Opinion statement  The standard therapy for hairy cell leukemia (HCL) is with the nucleoside analogs, 2’-deoxycoformycin (dCF) or 2-chlorodeoxyadenosine\\u000a (CdA), which produce morphologic complete remissions (CRs) in the majority of patients, although residual hairy cells can\\u000a frequently be detected by molecular or immunologic techniques. Relapses continue to occur over time, but most patients respond\\u000a well to retreatment withthe same agent. The

Lynn Savoie; James B. Johnston

2001-01-01

3

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

4

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

5

Hairy cell leukemia masquerading as infective endocarditis.  

PubMed

Hairy cell leukemia is a chronic lymphoproliferative disorder affecting middle-aged adults, with the median age of 50-55 years. We report a case of hairy cell leukemia who presented with fever, splinter haemorrhages and moderate splenomegaly, simulating infective endocarditis. There was bicytopenia at presentation and hairy cells were seen in the peripheral blood. PMID:24426343

Ramasamy, Chandramohan; Dubashi, Biswajit; Rekha, J Sree; Basu, Debdatta; Jain, Ankit; Dutta, Tarun Kumar

2013-06-01

6

Hairy cell leukemia  

MedlinePLUS

... B cells, a type of white blood cell (lymphocyte). ... Kantarjian H, O’Brien S. The chronic leukemias. In Goldman L, Schafer AI, eds. Cecil Medicine . 24th ed. Philadelphia, PA: Saunders Elsevier; 2011:chap 190. National Comprehensive Cancer Network. ...

7

Treatment Options for Hairy Cell Leukemia  

MedlinePLUS

... marrow makes too many lymphocytes (a type of white blood cell). Hairy cell leukemia is a cancer ... other substances to all tissues of the body. White blood cells that fight infection and disease. Platelets ...

8

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

9

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

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

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

13

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

14

BRAF MUTATIONS IN HAIRY CELL LEUKEMIA  

PubMed Central

Background Hairy cell leukemia (HCL) is a well defined clinico-pathological entity whose underlying genetic lesion is still obscure. Methods We searched for HCL-associated mutations by massively parallel sequencing of the whole exome of leukemic and matched normal mononuclear cells purified from the peripheral blood of one patient with HCL. Results Whole exome sequencing identified 5 missense somatic clonal mutations that were confirmed at Sanger sequencing, including a heterozygous V600E mutation involving the BRAF gene. Since the BRAF V600E mutation is oncogenic in other tumors, further analyses were focused on this genetic lesion. Sanger sequencing detected mutated BRAF in 46/46 additional HCL patients (47/47 including the index case; 100%). None of the 193 peripheral B-cell lymphomas/leukemias other than HCL that were investigated carried the BRAF V600E mutation, including 36 cases of splenic marginal zone lymphomas and unclassifiable splenic lymphomas/leukemias. Immunohistological and Western blot studies showed that HCL cells express phospho-MEK and phospho-ERK (the downstream targets of the BRAF kinase), indicating a constitutive activation of the RAF-MEK-ERK mitogen-activated protein kinase pathway in HCL. In vitro incubation of BRAF-mutated primary leukemic cells from 5 HCL patients with PLX-4720, a specific inhibitor of active BRAF, led to marked decrease of phosphorylated ERK and MEK. Conclusions The BRAF V600E mutation was present in all HCL patients investigated. This finding may have relevant implications for the pathogenesis, diagnosis and targeted therapy of HCL (Funded by the Associazione Italiana Ricerca Cancro and others).

Tiacci, Enrico; Trifonov, Vladimir; Schiavoni, Gianluca; Holmes, Antony; Kern, Wolfgang; Martelli, Maria Paola; Pucciarini, Alessandra; Bigerna, Barbara; Pacini, Roberta; Wells, Victoria; Sportoletti, Paolo; Pettirossi, Valentina; Mannucci, Roberta; Elliott, Oliver; Liso, Arcangelo; Ambrosetti, Achille; Pulsoni, Alessandro; Forconi, Francesco; Trentin, Livio; Semenzato, Gianpietro; Inghirami, Giorgio; Capponi, Monia; Di Raimondo, Francesco; Patti, Caterina; Arcaini, Luca; Musto, Pellegrino; Pileri, Stefano; Haferlach, Claudia; Schnittger, Susanne; Pizzolo, Giovanni; Foa, Robin; Farinelli, Laurent; Haferlach, Torsten; Pasqualucci, Laura; Rabadan, Raul; Falini, Brunangelo

2013-01-01

15

Chemo-immunotherapy for hairy cell leukemia  

PubMed Central

With the introduction of the nucleoside analogs cladribine and pentostatin the treatment of patients with hairy cell leukemia (HCL) has been revolutionized, and the majority of patients achieve a long-lasting complete remission with rare patients ever needing the traditional treatment strategies such as splenectomy. However, in the studies employing either of these nucleoside analogs, a proportion of patients do not respond to the initial therapy and the event-free survival curve does not reach a plateau, with up to 40% of patients relapsing within a few years. New therapeutic modalities including monoclonal antibodies such as rituximab and immunotoxins such as BL22 are now available. Furthermore, progress in the identification of minimal residual disease (MRD) using consensus primer or patient specific polymerase chain reaction for the immunoglobulin heavy chain variable region gene (IGHV), as well as multiparameter flow cytometry, allows for the detection and eradication of MRD. Whether this will translate to a reduction in the rate of relapse will require large prospective randomized trials. Alternatively, it may be possible to identify patients who are more likely to relapse using pretreatment characteristics such as the mutational status of IGHV and apply these strategies solely to them.

RAVANDI, FARHAD

2014-01-01

16

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.

17

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.

18

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

19

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

20

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

21

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

22

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

23

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

24

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

25

Hairy Cell Leukemia: Similarity of Cell Surface Characteristics from Multiple Sites in Three Patients.  

National Technical Information Service (NTIS)

In three patients with hairy cell leukemia (HCL), the similarity of the surface ultrastructure of cells from multiple sites was studied. These sites included peripheral blood and spleen in one patient, and peripheral blood and bone marrow in two patients....

H. M. Golomb D. Simon

1977-01-01

26

[Molecular and therapeutic advances in Hairy cell leukemia].  

PubMed

Hairy cell leukemia is a rare chronic lymphoproliferative disorder. Its diagnosis remains difficult due to different variant forms and differential diagnosis that are splenic marginal zone lymphoma and b-prolymphocytic leukemia. The prognosis of this malignancy has been transformed by purine nucleoside analogs, interferon, monoclonal antibodies and recombinant immunotoxins usually used in refractory or relapsed disease. The discovery of BRAF V600E mutation has become the milestone in the disease's history since it was uniformly identified in a HCL series in 2011. This mutation, commonly identified in melanoma, involves the protooncogene BRAF, a MAP3Kinase belonging to the RAF-MEK-ERK signaling pathway, which is the central key in several oncogenic processes. This mutation suggests disease-specific oncogene dependence. The detection of this mutation provides an additional diagnosis marker (because not found in variant forms), a best for monitoring minimal residual disease and a therapeutic target with the BRAF inhibitors in specific subgroups of patients, already tested in melanoma. This review aims to summarize the clinical and biological aspects and treatment of hairy cell leukemia and discusses the perspectives provided by the discovery of BRAF mutation in this disease. PMID:24103785

Balsat, Marie; Cornillon, Jérôme

2013-10-01

27

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

28

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

29

General Information about Hairy Cell Leukemia  

MedlinePLUS

... The cells are stained with a light-sensitive dye , placed in a fluid , and passed in a ... measurements are based on how the light-sensitive dye reacts to the light. Cytogenetic analysis : A laboratory ...

30

Effective Treatment of a Refractory Hairy Cell Leukemia Variant with Splenic Pre-Irradiation and Alemtuzumab  

Microsoft Academic Search

A 72-year-old Japanese man presented with 43.1 × 109\\/l hairy cells and apparent splenomegaly. The leukemia cells had unevenly distributed microvilli and round nuclei with dense chromatin and one or two clear nucleoli, lacked CD25 expression and were negative for tartrate-resistant acid phosphatase. The case was diagnosed as hairy cell leukemia variant (HCLv) and proved refractory to various chemotherapies, including

Makoto Sasaki; Koichi Sugimoto; Takeshi Mori; Kumiko Karasawa; Kazuo Oshimi

2008-01-01

31

Evidence of canonical somatic hypermutation in hairy cell leukemia  

PubMed Central

To compare hairy cell leukemia (HCL) with chronic lymphocytic leukemia (CLL) and normal B cells with respect to their B-cell receptors, somatic hypermutation (SHM) features in HCL were examined in a series of 130 immunoglobulin gene heavy chain rearrangements, including 102 from 100 classic (HCLc) and 28 from 26 variant (HCLv) patients. The frequency of unmutated rearrangements in HCLc was much lower than that in HCLv (17% vs 54%, P < .001) or historically in CLL (17% vs 46%, P < .001), but HCLv and CLL were similar (P = .45). As previously reported for CLL, evidence of canonical SHM was observed in HCLc rearrangements, including: (1) a higher ratio of replacement to silent mutations in the complementarity determining regions than in the framework regions (2.83 vs 1.41, P < .001), (2) higher transition to transversion ratio than would be expected if mutations were random (1.49 vs 0.5, P < .001), and (3) higher than expected concentration of mutations within RGYW hot spots (13.92% vs 3.33%, P < .001). HCLv met these 3 criteria of canonical SHM to a lesser extent. These data suggest that, whereas HCLc cells may recognize antigen-like CLL and normal B cells before malignant transformation, HCLv cells from some patients may originate differently, possibly without undergoing antigen recognition.

Arons, Evgeny; Roth, Laura; Sapolsky, Jeffrey; Suntum, Tara; Stetler-Stevenson, Maryalice

2011-01-01

32

Evidence of canonical somatic hypermutation in hairy cell leukemia.  

PubMed

To compare hairy cell leukemia (HCL) with chronic lymphocytic leukemia (CLL) and normal B cells with respect to their B-cell receptors, somatic hypermutation (SHM) features in HCL were examined in a series of 130 immunoglobulin gene heavy chain rearrangements, including 102 from 100 classic (HCLc) and 28 from 26 variant (HCLv) patients. The frequency of unmutated rearrangements in HCLc was much lower than that in HCLv (17% vs 54%, P < .001) or historically in CLL (17% vs 46%, P < .001), but HCLv and CLL were similar (P = .45). As previously reported for CLL, evidence of canonical SHM was observed in HCLc rearrangements, including: (1) a higher ratio of replacement to silent mutations in the complementarity determining regions than in the framework regions (2.83 vs 1.41, P < .001), (2) higher transition to transversion ratio than would be expected if mutations were random (1.49 vs 0.5, P < .001), and (3) higher than expected concentration of mutations within RGYW hot spots (13.92% vs 3.33%, P < .001). HCLv met these 3 criteria of canonical SHM to a lesser extent. These data suggest that, whereas HCLc cells may recognize antigen-like CLL and normal B cells before malignant transformation, HCLv cells from some patients may originate differently, possibly without undergoing antigen recognition. PMID:21368287

Arons, Evgeny; Roth, Laura; Sapolsky, Jeffrey; Suntum, Tara; Stetler-Stevenson, Maryalice; Kreitman, Robert J

2011-05-01

33

Minimal Residual Disease in Hairy-cell Leukemia after Treatment with 2-chlorodeoxyadenosine  

Microsoft Academic Search

ABSTRACTSome patients in apparent complete remission of hairy cell leukemia (HCL) after 2-chlorodeoxyadenosine (2-CdA) treatment may have minimal residual disease (MRD). This study examines detection of minimal residual disease by immunohistological staining using the monoclonal antibody (MoAb) B-ly 7 in 11 patients with complete remission of hairy cell leukemia (HCL) after 2-CdA therapy between 1990 and 1993. In all 11

Günther Konwalinka; Michael Schirmer; Wolfgang Hilbe; Falko Fend; Francoise Geisen; Anton Knoblechner; Andreas Petzer; Josef Thaler

1995-01-01

34

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

SciTech Connect

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 evidence of infiltrating hairy cells; he is still in complete remission four years after transplantation. In contrast to other patients with this disorder, he has had no predisposition to infections since transplantation. These results demonstrate that hairy-cell leukemia is sensitive to high-dose cytotoxic therapy and is not associated with any microenvironmental abnormalities that prevent repopulation with normal stem cells. Thus, high-dose chemoradiotherapy followed by bone-marrow transplantation is an effective and potentially curative therapy for hairy-cell leukemia. (JMT)

Cheever, M.A. (Univ. of Washington, Seattle); Fefer, A.; Greenberg, P.D.; Appelbaum, F.; Armitage, J.O.; Buckner, C.D.; Sale, G.E.; Storb, R.; Witherspoon, R.P.; Thomas, E.D.

1982-08-01

35

Hairy cell leukemia-new genes, new targets.  

PubMed

Hairy cell leukemia (HCL), a B cell malignancy comprising 2 % of all leukemias, has become quite exciting recently with regard to the development of new targets for therapy. This review will focus on advancements made within the past 1-2 years in targeted therapy for this disease. These advances may be grouped into two very difference categories, namely targeting of CD22 with the recombinant immunotoxin moxetumomab pasudotox, and targeting of the mutated BRAF component of the MAP kinase pathway. Moxetumomab pasudotox in phase I testing was recently reported to be associated with an overall response rate of 86 % and a complete remission (CR) rate of 46 % in 28 patients with relapsed and refractory HCL. Many of the CRs are without minimal residual disease (MRD). Severe or dose limiting toxicity was not observed on this trial, but a completely reversible and largely asymptomatic form of grade 2 hemolytic uremic syndrome occurred in two patients during retreatment. This agent has commenced phase III multicenter testing to validate its phase I results. An extensive number of studies have documented the V600E mutation in nearly all HCL patients, but not in similar hematologic malignancies. The thymidine kinase inhibitor vemurafenib, which inhibits the V600E mutant of BRAF, was reported to induce a CR in multiply relapsed and refractory HCL, with nearly complete clearing of MRD. One additional partial and one additional complete remission were subsequently reported. PMID:23892906

Kreitman, Robert J

2013-09-01

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

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

40

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

41

The hairy cell leukemia cell line Eskol spontaneously synthesizes tumor necrosis factor- ? and nitric oxide  

Microsoft Academic Search

Tumor necrosis factor-? (TNF-?) and nitric oxide (NO) exert a wide array of immunoregulatory, partly related effects. We examined the production of these two mediators by the human hairy cell leukemia cell line Eskol. Combined cell lysate and supernatant of Eskol cells (0.5×106 cells ml?1) incubated for 18 h, contained a mean of 1.5 ng ml?1 TNF-?. This spontaneous TNF-?

Andreas Eigler; Kerstin Waller-Fontaine; Jochen Moeller; Gunther Hartmann; Ulrich T Hacker; Stefan Endres

1998-01-01

42

Constant activation of the RAF-MEK-ERK pathway as a diagnostic and therapeutic target in hairy cell leukemia  

PubMed Central

The BRAF-V600E mutation defines genetically hairy cell leukemia among B-cell leukemias and lymphomas. In solid tumors, BRAF-V600E is known to aberrantly activate the oncogenic MEK-ERK pathway, and targeted BRAF and/or MEK inhibitors have shown remarkable efficacy in clinical trials in melanoma patients. However, the MEK-ERK pathway status in hairy cell leukemia has not been thoroughly investigated. We assessed phospho-ERK expression in 37 patients with hairy cell leukemia and 44 patients with neoplasms mimicking hairy cell leukemia (40 splenic marginal zone lymphoma, 2 hairy cell leukemia-variant and 2 splenic lymphoma/leukemia unclassifiable) using immunohistochemistry on routine biopsies and/or Western blotting on purified leukemic cells, and correlated the phospho-ERK status with the BRAF-V600E mutation status. Besides confirming the constant presence of BRAF-V600E in all patients with hairy cell leukemia, we observed ubiquitous phospho-ERK expression in this malignancy. Conversely, all 44 cases with neoplasms mimicking hairy cell leukemia were devoid of BRAF-V600E and none expressed phospho-ERK. Furthermore, the two exceptionally rare cases of non-hairy cell leukemia unclassifiable chronic B-cell neoplasms previously reported to be BRAF-V600E+ on allele-specific polymerase chain reaction lacked phospho-ERK expression as well, suggesting the presence of the mutation in only a small part of the leukemic clone in these cases. In conclusion, our findings support the use of phospho-ERK immunohistochemistry in the differential diagnosis between hairy cell leukemia and its mimics, and establish the MEK-ERK pathway as a rational therapeutic target in this malignancy.

Tiacci, Enrico; Schiavoni, Gianluca; Martelli, Maria Paola; Boveri, Emanuela; Pacini, Roberta; Tabarrini, Alessia; Zibellini, Silvia; Santi, Alessia; Pettirossi, Valentina; Fortini, Elisabetta; Ascani, Stefano; Arcaini, Luca; Inghirami, Giorgio; Paulli, Marco; Falini, Brunangelo

2013-01-01

43

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.

44

Soluble interleukin-2 receptor in hairy-cell leukemia: a reliable marker of disease.  

PubMed

The CD25 molecule, which corresponds to the p55 alpha chain of the interleukin-2 receptor, is strongly expressed by neoplastic cells in hairy-cell leukemia and is released in large amounts in the soluble form which is detectable in serum. In order to assess the reliability of the soluble interleukin-2 receptor as a disease marker in the management of patients with hairy-cell leukemia, we investigated serum levels in 35 untreated patients and in 2 patients with the hairy-cell leukemia variant. In 21 of 35 patients soluble receptor levels were also monitored during and after recombinant interferon-alpha therapy. Clinical and hematological parameters were also assessed. Soluble interleukin-2 receptor levels were extremely high at the time of diagnosis in patients with typical hairy-cell leukemia [32,722 +/- 27,001 vs. 331 +/- 145 units/ml in controls (mean +/- SD)], but not in patients with the leukemia variant. A progressive decrease in soluble interleukin-2 receptor levels paralleled the clinical response to treatment, although normal values were never detected, even in patients who achieved an apparent complete remission. After recombinant interferon-alpha discontinuation, disease recurrence was accompanied by a progressive increase to pre-treatment soluble receptor levels. Overall, a close correlation was found between soluble interleukin-2 receptor values and total tumor burden (r = 0.84, P < 0.001). On the basis of these data, soluble interleukin-2 receptor should be regarded as a key marker in the management of patients with hairy-cell leukemia. PMID:8477089

Ambrosetti, A; Nadali, G; Vinante, F; Ricetti, M M; Todeschini, G; Morosato, L; de Sabata, D; Bergamo Andreis, I A; Chilosi, M; Semenzato, G

1993-01-01

45

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

PubMed

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

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

2013-04-01

46

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

47

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

48

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

49

Treatment of hairy cell leukemia patients with 2-chloro-2'-deoxyadenosine (2-CdA).  

PubMed

A preliminary study of six hairy cell leukemia patients treated with one course of 2-chloro-2'-deoxyadenosine (2-CdA) is presented. 2-CdA was administered 0.1 mg/kg/daily by intravenous infusion over 7 days. Two patients achieved CR and four PR. PMID:7503630

Komarnicki, M; Ka?mierczak, M; Hansz, J

1994-01-01

50

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

51

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

52

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

53

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

54

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

55

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

56

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

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, 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

58

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

59

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

60

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

61

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

62

Importance of minimal residual disease in hairy cell leukemia: monoclonal antibodies as a therapeutic strategy  

PubMed Central

With the use of nucleoside analogs as frontline therapy, the prognosis of hairy cell leukemia (HCL) has improved dramatically. Unfortunately, disease recurrence remains problematic. Eradication of minimal residual disease (MRD) persisting after therapy may further improve outcome. The evolution of available techniques used to assess MRD, and the potential incorporation of novel agents such as monoclonal antibodies (MoAbs) into the treatment armamentarium for HCL mandate that MRD analyses be performed concurrently with routine assessments of disease status. Herein, the available data regarding the prevalence and clinical relevance of MRD after therapy for HCL is reviewed.

THOMAS, DEBORAH A.; RAVANDI, FARHAD; KEATING, MICHAEL; KANTARJIAN, HAGOP M.

2014-01-01

63

A Novel CD11c Monoclonal Antibody Effective in Formalin-Fixed Tissue for the Diagnosis of Hairy Cell Leukemia  

Microsoft Academic Search

Objective: The diagnosis of hairy cell leukemia (HCL) and its distinction from other B-cell lymphomas can be difficult in formalin-fixed tissue. This is because the histology is not always classical, and despite having a characteristic phenotype, there are few relevant monoclonal antibodies with sufficient sensitivity and specificity that can be applied to fixed material. In this study, we assessed the

Korinna Jöhrens; Lisa C. Happerfield; John P. Brown; Wendy N. Erber; Harald Stein; Ioannis Anagnostopoulos

2008-01-01

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

A Case of Primary Plasma Cell Leukemia with Hairy-cell Morphology and Lambda-type Bence-Jones Protein. Immunohistochemical and Molecular Analysis  

Microsoft Academic Search

A case of primary plasma cell leukemia with hairy-cell morphology and lambda-type Bence- Jones protein is reported. Most of the atypical cells in the peripheral blood of this case were small lymphoid cells or lymphoplasmacytoid lymphocytes with numerous cytoplasmic hairy projections. Plasmablastic cells and 'tadpole'-like cells were also present in the bone marrow. Immunohistochemically, these atypical cells expressed the cytoplasmic

Fumihiko Tanioka; Sadahiro Tamashima; Shin-ichi Shimizu; Hiroshi Kobayashi; Yukio Kobayashi

68

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

69

Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia  

PubMed Central

We conducted this study to determine the feasibility and safety of cladribine followed by rituximab in patients with hairy cell leukemia including the vari-ant form (HCLv). Cladribine 5.6 mg/m2 given IV over 2 hours daily for 5 days was followed ? 1 month later with rituximab 375 mg/m2 IV weekly for 8 weeks. Responses were recorded and BM minimal residual disease (MRD) was evaluated after the completion of rituximab. Thirty-six patients have been treated including 5 with HCLv. Median age was 57 years (range, 37-89). All patients (100%) have achieved complete response (CR), defined as presence of no hairy cells in BM and blood with normalization of counts (absolute neutrophil count [ANC]> 1.5 × 109/L, hemoglobin [Hgb] > 12.0 g/dL, platelets [PLT] > 100 × 109/L), as well as resolution of splenomegaly. There were no grade 3 or 4 nonhematologic adverse events directly related to the treatment. Only 1 patient (with HCLv) has relapsed; median CR duration has not been reached (range,1+-63+ months). Three patients with HCLv died including 1 with relapsed disease and 2 from unrelated malignancies. Median survival duration has not been reached (range, 2+-64+ months). Treatment with clad-ribine followed by rituximab is effective tk;4and may increase CR rate. This study was registered at www.clinicaltrials.gov as NCT00412594.

O'Brien, Susan; Jorgensen, Jeffrey; Pierce, Sherry; Faderl, Stefan; Ferrajoli, Alessandra; Koller, Charles; Challagundla, Pramoda; York, Sergernne; Brandt, Mark; Luthra, Rajyalakshmi; Burger, Jan; Thomas, Deborah; Keating, Michael; Kantarjian, Hagop

2011-01-01

70

[Variant hairy-cell leukemia: immunophenotypic and ultrastructural study of a case].  

PubMed

The recent introduction of new methods to identify different lymphocytic subsets has made it possible to recognise a rare variant of the classic hairy cell leukaemia, showing intermediate features between prolymphocytic leukaemia and hairy cell leukaemia. A 37-year-old patient is reported who followed a mildly aggressive clinical course and had massive splenomegaly without lymph node enlargement. Moderate leucopenia with lymphocytosis was present, with frequent hairy cells carrying one prominent nucleole. The cytochemical pattern include tartrate-sensitive acid phosphatase positivity, and the immunophenotype of such cells was CD22++, CD11++, CD24-, CD25-, CD2-, CD5-, CD19++. No lamellar ribosomal complex was seen in the ultrastructural study of the hairy cells. The patient was diagnosed as having variant hairy cell leukaemia and achieved partial response after splenectomy. The clinical, diagnostic and therapeutic aspects of this rare variant are discussed. PMID:1866652

Palomera, L; García Díez, I; Martínez García, R

1991-04-01

71

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

72

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

73

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

74

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

75

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

76

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

77

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

78

Severe deficiency of natural killer activity in the peripheral blood of patients with hairy cell leukemia.  

PubMed

Natural killer (NK) activity against K-562 tumor cells was evaluated in peripheral blood leukocytes (PBL) obtained from untreated patients affected by hairy cell leukemia (HCL). NK activity present in PBL from 10 HCL patients was at least six-fold lower (p less than 0.01) than that present in PBL from 15 healthy donors. Decreased NK activity in HCL PBL was not due to dilution of the NK effector cells by the neoplastic cells; in fact, NK activity of PBL from 4 HCL patients with less than 5% circulating neoplastic cells was still five-fold lower (p less than 0.01) than that present in normal PBL. Partial characterization of the NK defect in HCL patients indicated that: (A) defective cytotoxicity was not dependent on the duration of the assay; (B) HCL PBL added to normal PBL during the assay did not exert suppressor activity; (C) the NK activity of HCL PBL could be potentiated in vitro by interferon; and (D) low levels of NK activity were associated with reduced numbers of circulating monocytes (p less than 0.01) and of large granular lymphocytes (LGL) (p less than 0.01). In conclusion, our results indicate that the low levels of NK activity present in the peripheral blood of HCL patients may be related to reduced numbers of circulating effector cells. PMID:6220750

Ruco, L P; Procopio, A; Maccallini, V; Calogero, A; Uccini, S; Annino, L; Mandelli, F; Baroni, C D

1983-06-01

79

High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias.  

PubMed

To understand the genetic mechanisms driving variant and IGHV4-34-expressing hairy-cell leukemias, we performed whole-exome sequencing of leukemia samples from ten affected individuals, including six with matched normal samples. We identified activating mutations in the MAP2K1 gene (encoding MEK1) in 5 of these 10 samples and in 10 of 21 samples in a validation set (overall frequency of 15/31), suggesting potential new strategies for treating individuals with these diseases. PMID:24241536

Waterfall, Joshua J; Arons, Evgeny; Walker, Robert L; Pineda, Marbin; Roth, Laura; Killian, J Keith; Abaan, Ogan D; Davis, Sean R; Kreitman, Robert J; Meltzer, Paul S

2014-01-01

80

Variables in the Quantification of CD4 in Normals and Hairy Cell Leukemia Patients  

PubMed Central

Background Quantitative flow cytometry (QFCM) is being applied in the clinical flow cytometry laboratory. Quantitative normal T-cell CD4 expression represents a biologic standard and quality control agent. However, low levels of CD4 expression were detected in normal T-cells in Hairy Cell Leukemia (HCL) samples. Methods The QuantiBrite System® was used to determine the level of CD4 expression (mean antibody bound per cell, ABC) in fresh and shipped HCL blood and fresh normal donor blood (NDB). The effects of shipping, lysing reagent, cell preparation method and antibody lot were evaluated. Results Shipped HCL specimens (n = 69) had a significantly lower mean CD4 ABC of 38,788 (CV = 9.1%) compared to fresh specimens (n = 105) CD4 value of 40,330 (CV = 8.4%) (p < 0 .05). In NDB, significant differences were seen for fresh versus shipped specimens using the stain/lyse method but not for lyse/stain method. Consistent differences in CD4 ABC based upon antibody lot were observed in fresh HCL and NDB samples. Stain/lyse and lyse/stain methods using NH4Cl lyse were compared in NDB using identical samples and antibodies. The NDB CD4 ABC values obtained with the lyse (NH4Cl )/stain method (45,562, 3.7% CV) were lower than those obtained with the stain/lyse (NH4Cl) method (49,955, 3.3% CV) with p<0.001. Conclusions CD4 expression in HCL patient samples is not inherently different from that observed in NDB and therefore may serve as a biological control in clinical QFCM. Technical variables impact significantly on QFCM of CD4.

Wang, Lili; Abbasi, Fatima; Jasper, Gregory A; Kreitman, Robert J; Liewehr, David; Marti, Gerald E.; Stetler-Stevenson, Maryalice

2010-01-01

81

Soluble CD22 as a tumor marker for hairy cell leukemia  

PubMed Central

CD22 is an important immunotherapeutic target on B-cell malignancies, particularly hairy cell leukemia (HCL), but its soluble extracellular domain, sCD22, has not yet been reported in the blood. By immunoaffinity and enzyme-linked immunosorbent assay techniques using anti-CD22 monoclonal antibodies, we identified the 100-kDa extracellular domain of CD22 and an 80-kDa processed form in serum of patients with HCL. The median sCD22 level measured by enzyme-linked immunosorbent assay was 18 ng/mL for 93 patients with HCL. sCD22 levels varied from 2.1 to 163 ng/mL and were higher (P < .001) than 23 normal donors (median, 0.6 ng/mL). More than 95% of normal donors had sCD22 levels less than 1.9 ng/mL. sCD22 levels were proportional to concentrations of circulating HCL cells (P = .002), and HCL spleen size (P < .001). sCD22 levels normalized with complete but not partial response to treatment. sCD22 levels up to 300 ng/mL had less than a 2-fold effect on the cytotoxicity of the anti-CD22 recombinant immunotoxin BL22. sCD22 levels may be useful to follow in patients with HCL and may be more specific than sCD25 in patients with CD22+/CD25? disease. Trials are listed on www.cancer.gov as NCT00002765, NCT00021983, NCT00074048, NCT00085085, NCT00337311, and NCT00462189.

Matsushita, Kakushi; Margulies, Inger; Onda, Masanori; Nagata, Satoshi; Stetler-Stevenson, Maryalice

2008-01-01

82

Treatment of hairy cell leukemia with deoxycoformycin (YK-176). The Deoxycoformycin (YK-176) Study Group.  

PubMed

Eleven patients with hairy cell leukemia (HCL) were treated with YK-176 (2'-deoxycoformycin) at a dose of 5 mg/m2 by intravenous injection every week or every other week. Patients received a median of eight (range 4-19) injections of YK-176. Five patients had previously been untreated, four of whom had massive splenomegaly. Six patients had previously been treated, four with interferon-alpha (IFN-alpha) or IFN-alpha and chemotherapy and two with prednisolone. Two patients had had splenectomies. Five patients achieved complete remission (CR) and six, partial remission (PR) according to WHO criteria (remission rate 100%, 95% confidence interval (CI) 74-100%). All six neutropenic patients recovered > 1,500/microliters neutrophils, six of seven anemic patients recovered > 12.0 g/dl hemoglobin and five of nine thrombocytopenic patients recovered > 100,000/microliters platelets following the treatment. According to the response criteria for HLC, five patients achieved CR, two PR and four minor response. The overall remission (CR + PR) rate was 64% (95% CI 35-85%). The CR and PR have lasted from > 30 to > 718 days (median, > 281 days) so far with no relapses. Of four patients previously treated with IFN-alpha, two achieved CR and one, PR. All patients were alive with a median survival time of > 290 days from treatment (range > 50- > 763 days). The treatment was generally well tolerated. Mild to moderate nausea, vomiting, appetite loss and general fatigue were experienced in two patients, skin rash in one and a transient fever in three. YK-176 was a highly active agent in the treatment of HCL. PMID:1291757

Shimoyama, M; Tobinai, K; Yamaguchi, K; Hirashima, K; Itoh, S; Konishi, H; Mikuni, C; Togawa, A; Hotta, T; Toyoda, N

1992-12-01

83

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

84

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

85

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

86

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

87

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

88

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

89

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

90

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

91

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

92

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

93

Disruption of a novel ectodermal neural cortex 1 antisense gene, ENC1AS and identification of ENC1 overexpression in hairy cell leukemia  

Microsoft Academic Search

Karyotypical alteration of chromosome 5 and in particular band 5q13 is a frequent finding in hairy cell leukemia (HCL). We have previously identified a number of candidate genes localized in close proximity to a constitutional inv(5)(p13.1q13.3) breakpoint in one HCL patient. These included beta-hexosaminodase HEXB, frequently mutated in the lysosomal storage disorder Sandhoff disease. We now report that the 5q13.3

Marianne Hammarsund; Mikael Lerner; Chaoyong Zhu; Mats Merup; Monika Jansson; Gosta Gahrton; Hanneke Kluin-Nelemans; Stefan Einhorn; Dan Grander; Olle Sangfelt; Martin Corcoran

2004-01-01

94

CD11c gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras and junD  

Microsoft Academic Search

Hairy cell leukemia (HCL) is a chronic lym- phoproliferative disease, the cause of which is unknown. Diagnostic of HCL is abnormal expression of the gene that encodes the 2 integrin CD11c. In order to determine the cause of CD11c gene expression in HCL the CD11c gene promoter was characterized. Transfection of the CD11c promoter linked to a luciferase reporter gene

Fotini Nicolaou; Jens M. Teodoridis; Alexander Georgakis; Omid C. Farokhzad; Erwin P. Bottinger; Philippe Rousselot; Christine Chomienne; Katalin Ferenczi; M. Amin Arnaout; C. Simon Shelley

2003-01-01

95

Variant B Cell Receptor Isotype Functions Differ in Hairy Cell Leukemia with Mutated BRAF and IGHV Genes  

PubMed Central

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 Ca2+ 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.

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

2014-01-01

96

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

97

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

98

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

99

Hairy cell leukemia: epidemiology, pharmacokinetics of cladribine, and long-term follow-up of subcutaneous therapy.  

PubMed

Hairy cell leukemia is often reported as a disease of young males. The male predominance is strong, 4:1, but the median age in the Swedish national compulsory cancer registry is similar to that of follicular lymphoma, i.e. 62 years. The overall 6-year survival in the Swedish registry of patients diagnosed since 2000 is 80%, 93% of patients <60 years, and 68% of those >60 years. The yearly risk of secondary cancers is 1.75%. Cladribine is a prodrug which is selectively activated intracellularly. The intracellular initial half-life is 13?h and the terminal half-life is 30?h. Subcutaneous injection once daily is simple and effective due to 100% bioavailability and no local side effects from injection, and self-administration is easy. Long-term follow-up of Scandinavian patients treated with cladribine (mostly as subcutaneous injections) in the early 1990s shows a >80% 15-year survival from cladribine treatment in <60 years of age, but? <50% in older patients. Survival from diagnosis of these patients was similar for those previously treated and untreated. PMID:21599605

Juliusson, Gunnar; Samuelsson, Henrik

2011-06-01

100

Hairy cell leukemia: clinical presentation and long term follow up after treatment with 2-chlorodeoxyadenosine (2-CdA).  

PubMed

The aim of the study was to the clinical features and long term follow up after treatment with Cladarbine in a tertiary care hospital. Seven patients with hairy cell leukemia were diagnosed between January 1990 till December 2003. Diagnosis in all the patients was established by bone marrow aspirates and trephine biopsy along with TRAP. In two patients the diagnosis was supplemented by flowcytometry and in another two patients by splenectomy. Six patients were male while one was female. Mean age was 47.7 years (range 36-64). Most common presenting features were pallor and weakness (n=5). All patients had splenomegaly. Blood count at presentation revealed that one patient had bicytopenia, two had isolated thrombocytopenia, and three had pancytopenia. Treatment responses were evaluable in seven patients. Complete response was seen in six patients (85.7%). One patient died after two months due to sepsis while 3 (50%) patients relapsed. Those who relapsed received another course of CDA and have maintained remission with a median duration of response of 48 months (20-48). From this small series we can conclude that CDA is an effective treatment for HCL and even it works very well in relapsed cases. PMID:15960289

Bilwani, Fareena; Usman, Mohammad; Adil, Salman N; Kakepoto, Ghulam N; Khurshid, Mohammad

2005-05-01

101

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

102

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

103

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

104

Treating Hairy Cell Leukemia  

MedlinePLUS

... chemotherapy. Rituximab or interferon-alfa, a type of biologic therapy, may be helpful. If a patient is uncomfortable because of an enlarged spleen, removing the spleen by surgery (splenectomy) can often help relieve pain or other symptoms. Last Medical Review: 07/31/2013 Last Revised: 04/18/2014 ...

105

Hairy Cell Leukemia.  

National Technical Information Service (NTIS)

Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related ...

1986-01-01

106

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

PubMed

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

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

2013-02-01

107

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

108

2-chlorodeoxyadenosine (2-CdA) in 2-hour versus 24-hour intravenous infusion in the treatment of patients with hairy cell leukemia.  

PubMed

Forty one patients with hairy cell leukemia (HCL) were treated with 2-chloro-deoxyadenosine (2-CdA) administered in various schedules. Complete remission (CR) was achieved in 31 (76%) patients and partial remission (PR) in 9 (22%). The mean duration of remission (CR + PR) was 25.2 months (range 9-45 months). One patient did not respond to therapy. Twelve out of 16 patients (75%) achieved CR after 5-day intravenous infusions of 2-CdA and 19 out of 25 patients (76%) after 7-day courses. In 19 out of 23 patients (82.6%) CR was achieved after intermittent 2-hour infusions and in 12 out of 18 (66.7%) after continuous 24-hour infusion. The differences were not statistically significant. Side effects of 2-CdA were similar in both groups except for infections, which were less frequently observed in the group treated for 5 days. The results of our study suggest that 2-CdA can be effectively administered to patients with HCL using 5-day courses and a 2-hour daily infusion. PMID:8724536

Robak, T; B?asi?ska-Morawiec, M; Krykowski, E; Hansz, J; Komarnicki, M; Kazimierczak, M; Konopka, L; Maj, S; Hellmann, A; Zaucha, J M; Urasi?ski, L; Zdziarska, B; Kotlarek-Haus, S; Usnarska-Zubkiewicz, L; Kuratowska, Z; Dwilewicz-Trojaczek, J; Ho?owiecki, J; Krawczyk-Kulis, M; Grieb, P

1996-06-01

109

Leukemic Reticuloendotheliosis: 'Hairy Cell Leukemia,' Functional and Structural Features of the Abnormal Cell in a Patient with Profound Leukocytosis.  

National Technical Information Service (NTIS)

The development of profound leukocytosis in a patient with leukemic reticuloendotheliosis (LRE) enabled us to obtain purified LRE cells for the investigation of their structural and functional characteristics. The LRE cells of our patient bore surface imm...

D. H. Boldt S. F. Speckart R. P. MacDermott G. S. Nash J. E. Valeski

1976-01-01

110

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

PubMed Central

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

Nordstrom, M; Hardell, L; Lindstrom, G; Wingfors, H; Hardell, K; Linde, A

2000-01-01

111

Phase I Trial of Anti-CD22 Recombinant Immunotoxin Moxetumomab Pasudotox (CAT-8015 or HA22) in Patients With Hairy Cell Leukemia  

PubMed Central

Purpose To conduct a phase I dose-escalation trial assessing safety and response of recombinant immunotoxin moxetumomab pasudotox (CAT-8015, HA22) in chemotherapy-resistant hairy cell leukemia (HCL). Patients and Methods Eligible patients had relapsed/refractory HCL after ? two prior therapies and required treatment because of abnormal blood counts. Patients received moxetumomab pasudotox 5 to 50 ?g/kg every other day for three doses (QOD ×3), with up to 16 cycles repeating at ? 4-week intervals if patients did not experience disease progression or develop neutralizing antibodies. Results Twenty-eight patients were enrolled, including three patients each at 5, 10, 20, and 30 ?g/kg, four patients at 40 ?g/kg, and 12 patients at 50 ?g/kg QOD ×3 for one to 16 cycles each (median, four cycles). Dose-limiting toxicity was not observed. Two patients had transient laboratory abnormalities consistent with grade 2 hemolytic uremic syndrome with peak creatinine of 1.53 to 1.66 mg/dL and platelet nadir of 106,000 to 120,000/?L. Drug-related toxicities in 25% to 64% of the 28 patients included (in decreasing frequency) grade 1 to 2 hypoalbuminemia, aminotransferase elevations, edema, headache, hypotension, nausea, and fatigue. Of 26 patients evaluable for immunogenicity, 10 patients (38%) made antibodies neutralizing more than 75% of the cytotoxicity of 1,000 ng/mL of immunotoxin, but this immunogenicity was rare (5%) after cycle 1. The overall response rate was 86%, with responses observed at all dose levels, and 13 patients (46%) achieved complete remission (CR). Only 1 CR lasted less than 1 year, with the median disease-free survival time not yet reached at 26 months. Conclusion Moxetumomab pasudotox at doses up to 50 ?g/kg QOD ×3 has activity in relapsed/refractory HCL and has a safety profile that supports further clinical development for treatment of this disease.

Kreitman, Robert J.; Tallman, Martin S.; Robak, Tadeusz; Coutre, Steven; Wilson, Wyndham H.; Stetler-Stevenson, Maryalice; FitzGerald, David J.; Lechleider, Robert; Pastan, Ira

2012-01-01

112

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

113

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

114

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

115

T Cells and Natural Killer Cells after Treatment of Hairy Cell Leukaemia with 2-Chlorodeoxyadenosine  

Microsoft Academic Search

We report that continuous suppression of CD4+ lymphocyte subsets does not necessarily lead to an increased rate of infections more than 6 months after treatment of hairy cell leukemia (HCL) with 2-chlorodeoxyadenosine (cladribine; 2-CdA). In a retrospective analysis of 17 consecutive patients with HCL treated with 2-CdA and followed thereafter for an average of 440 days (ranging from 71 to

Michael Schirmer; Wolfgang Hilbe; Françoise Geisen; Josef Thaler; Günther Konwalinka

1997-01-01

116

Peroxidase production from carrot hairy root cell culture  

Microsoft Academic Search

Carrot hairy roots have shown vigorous growth and extensive lateral root branching in the absence of phytohormone. The production of peroxidase which was not detected in suspension cells was observed in high amounts in carrot hairy root. High peroxidase activity (19.2 Ug?1 fresh cell weight) was obtained by increasing the total phenolics concentration in the media. Peroxidase synthesis could be

Yong Hwan Kim; Young Je Yoo

1996-01-01

117

The clinico-hematological profile of hairy cell leukaemia: a single centre experience.  

PubMed

The response rates and overall survival of hairy cell leukemia has changed remarkably with cladribine. Twenty patients diagnosed as hairy cell leukemia over a 5 year period were evaluated. Median age of the patients was 52.5 years. Splenomegaly was seen in 85% and hepatomegaly in 50% patients. At presentation, pancytopenia was seen in 45% and bicytopenia in 20% patients. Tartrate resistant acid phosphatase was positive in 73.68%. Cladribine was given in 13 patients. Overall survival was 84.6%. Median duration of follow-up was 17 months (4-108 months). Direct Coombs' test positive autoimmune hemolytic anemia was seen in two patients (15.38%) on cladribine therapy who required treatment with steroids. PMID:20557675

Bhargava, Rahul; Kar, Rakhee; Mahapatra, Manoranjan; Saxena, Renu

2010-06-01

118

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

2014-05-30

119

Hairy cell leukaemia: a heterogeneous disease?  

PubMed Central

The US National Cancer Institute’s Surveillance, Epidemiology and End Results program was used to develop aetiological clues for hairy cell leukaemia (HCL). Descriptive techniques (age-adjusted incidence trends, age-specific incidence rates (IR), and age distributions-at-diagnosis) were supplemented with mathematical models (two-component mixture, generalized linear regression, and age-period-cohort). There were 2856 cases of HCL diagnosed during 1978–2004 (IR 0·32/100 000 person-years). IRs were nearly 4-fold greater among men than women and more than 3-fold higher for Whites than Blacks. Temporal trends were stable over time. Age-specific IRs increased rapidly until approximately 40 years then rose at a slower pace. The age-specific IR curves reflected bimodal early- and late-onset age distributions-at-diagnosis (or density plots), with some variation by gender. Among both men and women, a two-component mixture model fitted the data better than a single density or cancer population. Age-period-cohort models confirmed statistically significant age-related effects after full adjustment for temporal trends (calendar-period and birth-cohort effects). In summary, age incidence patterns (rates and bimodal densities) suggested that HCL is a heterogeneous disease, consisting of at least two underlying subgroups and/or cancer populations by age-at-onset. Distinct early- and late-onset HCL populations may reflect different age-related causal pathways, risk factor profiles, and/or stem cells of origin.

Dores, Graca M.; Matsuno, Rayna K.; Weisenburger, Dennis D.; Rosenberg, Philip S.; Anderson, William F.

2014-01-01

120

Diagnostic relevance of peripheral blood immunocytochemistry in hairy cell leukaemia.  

PubMed Central

AIMS--(1) To assess the diagnostic relevance of peripheral blood immunocytochemistry in hairy cell leukaemia (HCL); (2) to compare the immunostaining of bone marrow biopsy specimens with bone marrow and peripheral blood cytospins; (3) to evaluate the sensitivity of the different markers used; (4) to identify the ultrastructural localisation of DBA.44 in HCL variant. METHODS--Immunoenzymatic staining procedures, immunoperoxidase and immunoalkaline phosphatase, were used with a panel of monoclonal antibodies directed to HCL associated antigens. Ultrastructural immunostaining was performed using colloidal gold conjugated antibodies. RESULTS--HCL showed strong cytoplasmic reactivity for CD22, CD25, CD103, DBA.44, kappa, or lambda light chains. Peripheral blood diagnostic hairy cells were found in all the cases with absolute counts ranging from 0.11 x 10(9)/l up to 6.4 x 10(9)/l and values increasing with the size of the spleen. A median of 36.5% of leukaemic cells was found in bone marrow aspirates and 70% in bone marrow trephine specimens. The monoclonal antibodies CD22 and DBA.44 showed the highest and the lowest percentage of positive hairy cells, respectively; this difference was statistically significant (p = 0.0025). Ultrastructural immunolabelling with DBA.44 showed a cytoplasmic membrane localisation of the antigen in one case of HCL variant. CONCLUSIONS--(1) Immunocytochemistry is a useful technique which enhances the accuracy of diagnosis in HCL; (2) peripheral blood immunocytochemistry is recommended because it highlights hairy cells in all cases; (3) CD22 appears to be the most sensitive of the markers tested; (4) ultrastructural analysis is a useful tool in selected cases of HCL variant. Images

Cordone, I; Annino, L; Masi, S; Pescarmona, E; Rahimi, S; Ferrari, A; Giubilei, E; Pignoloni, P; Faraggiana, T; Mandelli, F

1995-01-01

121

Hairy-rod Complexes of Conjugated Polymers for Solar Cells  

NASA Astrophysics Data System (ADS)

The development of new high efficiency organic solar cells in many cases is largely predicated on the formation of ordered nanostructures in the active donor-acceptor layer. Hairy-rod conjugated polymers, consisting of a stiff conjugated backbone and flexible long side chains, self-assemble into ordered nanostructures via phase separation. In particular, they can form nematic, smectic and columnar phases depending on the volume fraction of side chains.[1] In combination with suitable second-phase semiconducting nanomaterials, they offer a potential route to the realization of ordered heterojunction devices. In this work, we report phase behaviors of novel hairy-rod complexes consisting of a polythiophene backbone with surfactant side chains. Two kinds of the complexes were prepared via ionic bonding: one contains the flexible hydrocarbon sequence in side chains whereas the other utilizes the rigid mesogenic moiety. The interactions between polythiophene and different surfactants were investigated. Phase transitions of the complexes were identified by a combination of various techniques including x-ray scattering and calorimetry. Both thermotropic and lyotropic liquid crystalline behaviors were observed. We discuss a simple model for the formation of the liquid crystalline mesophases in these supramolecular systems. Reference [1] R. Stepanyan, A. Subbotin, M. Knaapila, O. Ikkala, G. ten Brinke, Self-organization of hairy-rod polymers, Macromolecules, 2003, 36, 3758

Zhang, S.; Beach, E.; Anastas, P.; Pfefferle, L.; Osuji, C.

2010-03-01

122

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

123

Acute and Chronic Leukemia: Diagnosis, Treatment.  

National Technical Information Service (NTIS)

The Cancergram covers both acute and chronic leukemia in all of its forms (acute lymphocytic, acute monocytic, acute or sub-acute granulocytic, chronic granulocytic, chronic lymphocytic, chronic monocytic, plasma cell, stem cell, and hairy cell). Other ne...

1986-01-01

124

Acute and Chronic Leukemia: Diagnosis, Treatment.  

National Technical Information Service (NTIS)

The Cancergram covers both acute and chronic leukemia in all of its forms (acute lymphocytic, acute monocytic, acute or sub-acute granulocytic, chronic granulocytic, chronic lymphocytic, chronic monocytic, plasma cell, stem cell, and hairy cell). Other ne...

1983-01-01

125

Acute and Chronic Leukemia: Diagnosis, Treatment.  

National Technical Information Service (NTIS)

The Cancergram covers both acute and chronic leukemia in all of its forms (acute lymphocytic, acute monocytic, acute or sub-acute granulocytic, chronic granulocytic, chronic lymphocytic, chronic monocytic, plasma cell, stem cell, and hairy cell). Other ne...

1982-01-01

126

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

127

[Leukemia stem cell].  

PubMed

Cancer is the main cause of death in advanced countries. It has become progressively clear that cancer cells are distributed in a developmental hierarchy, in which whole cancer tissues originate from cancer stem cells(CSCs). CSCs were first discovered in a case of acute myeloid leukemia. Leukemia stem cells(LSCs)are resistant to conventional chemotherapies because of their dormancy and are therefore the cause of minimal residual disease and relapse. Many investigators are working to develop novel therapeutic strategies for eliminating LSCs. LSC biology is discussed in the first part of this review, and the therapeutic approach to LSC targeting is described in the latter part. PMID:24743272

Iwasaki, Hiromi

2014-03-01

128

Plasma cell leukemia  

Microsoft Academic Search

Plasma cell leukemia (PCL) is a rare, yet aggressive plasma cell (PC) neoplasm, variant of multiple myeloma (MM), characterized by high levels of PCs circulating in the peripheral blood. PCL can either originate de novo (primary PCL) or as a secondary leukemic transformation of MM (secondary PCL). Presenting signs and symptoms are similar to those seen in MM such as

Flavio Albarracin; Rafael Fonseca

2011-01-01

129

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

2014-01-10

130

Plasma cell leukemia with myelofibrosis  

Microsoft Academic Search

Summary We describe a case of plasma cell leukemia associated with myelofibrosis. A 60-year-old woman was admitted due to lumbago and monoclonal hypergammaglobulinemia. Peripheral blood showed about 40% of plasma-cell-like cells. A bone marrow aspiration was dry tap. The patient was diagnosed as having plasma cell leukemia with myelofibrosis by bone marrow biopsy. Plasma cell leukemia as well as myelofibrosis

T. Murayama; T. Matsui; Y. Hayashi; T. Taniguchi; M. Ito; T. Natazuka; S. Imoto; N. Iwata; T. Isobe; H. Ito; K. Chihara

1994-01-01

131

Diagnosis and Treatment of Acute and Chronic Leukemia.  

National Technical Information Service (NTIS)

The Cancergram covers both acute and chronic leukemia in all of its forms (acute lymphocytic, acute monocytic, acute or sub-acute granulocytic, chronic granulocytic, chronic lymphocytic, chronic monocytic, plasma cell, stem cell, and hairy cell). Other ne...

1977-01-01

132

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

Microsoft Academic Search

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

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

2000-01-01

133

Primary plasma cell leukemia  

Microsoft Academic Search

Four cases of primary plasma cell leukemia (PPCL) admitted to Zhongshan Hospital from 1959 to 1987 are reported with a review\\u000a on additional 40 cases reported in China. Comparing with the 57 cases of multiple myeloma (MM) treated in our hospital, the\\u000a following features were observed in PPCL: (1) The age was younger, with a mean of 45.2 years, 34.1%

Cai Zeji; Zhang Guozhen

1991-01-01

134

Plasma cell leukemia  

Microsoft Academic Search

Opinion statement  Plasma cell leukemia (PCL) is a rare aggressive variant of multiple myeloma (MM) characterized by a fulminant course and poor\\u000a prognosis. The median survival is measured in months. Therapy and prognosis partially depend on whether the disease presents\\u000a de novo or as a secondary process involving the leukemic transformation of a previously diagnosed MM. Secondary PCL represents\\u000a a terminal

Suzanne R. Hayman; Rafael Fonseca

2001-01-01

135

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

136

Scientists Report Complete Remissions in Early Leukemia Trial  

Cancer.gov

Scientists report in the New England Journal of Medicine that 11 of 13 patients with hairy cell leukemia, a cancer of the immune system, had complete remissions after receiving adequate treatment with the recombinant immunotoxin BL22

137

An interchangeable system of hairy root and cell suspension cultures ofCatharanthus roseus for indole alkaloid production.  

PubMed

Hairy roots ofCatharanthus roseus obtained by co-cultivation of hypocotyl segments withAgrobacterium rhizogenes, and cultured in SH (Schenk and Hildebrandt) basal medium, formed two types of calli when subcultured in SH medium with 1 mg/1 ?-naphthaleneacetic acid and 0.1 mg/l kinetin. One of them, a compact callus, when re-subcultured in SH basal medium gave rise to hairy roots again. A rhizogenic cell suspension culture was established from this type of callus. When cultured in SH medium with growth regulators, the rhizogenic callus produced catharanthine at a level of 41% of the level in the initial hairy roots. Upon transfer to SH basal medium, regenerated hairy roots produced this alkaloid at the original level of 1.5 mg/g dry wt. Using this cell/hairy root interchange system a new management system for hairy root culture in bioreactors has been devised and examined involving production of biomass in the form of a cell suspension in medium supplemented with growth regulators, and catharanthine production by hairy roots regenerated from these cells in medium without growth regulators. PMID:24185653

Jung, K H; Kwak, S S; Choi, C Y; Liu, J R

1995-01-01

138

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.

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

139

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

PubMed Central

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

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

2010-01-01

140

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.

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

2014-01-01

141

Plasma cell leukemia.  

PubMed

Plasma cell leukemia (PCL) is a rare, yet aggressive plasma cell (PC) neoplasm, variant of multiple myeloma (MM), characterized by high levels of PCs circulating in the peripheral blood. PCL can either originate de novo (primary PCL) or as a secondary leukemic transformation of MM (secondary PCL). Presenting signs and symptoms are similar to those seen in MM such as renal insufficiency, hypercalcemia, lytic bone lesions, anemia, and thrombocytopenia, but can also include hepatomegaly and splenomegaly. The diagnostic evaluation of a patient with suspected PCL should include a review of the peripheral blood smear, bone marrow aspiration and biopsy, serum protein electrophoresis (SPEP) with immunofixation, and protein electrophoresis of an aliquot from a 24h urine collection (UPEP). The diagnosis is made when a monoclonal population of PCs is present in the peripheral blood with an absolute PC count exceeding 2000/?L and PC comprising 20% or more of the peripheral blood white cells. The prognosis of PCL is poor with a median survival of 7 to 11 months. Survival is even shorter (2 to 7 months) when PCL occurs in the context of refractory or relapsing MM. There have been no prospective randomized trials investigating the treatment of PCL. Recommendations are primarily based upon data from small retrospective series, case reports, and extrapolation of data from patients with MM. In general, patients are treated with induction therapy followed by hematopoietic cell transplantation (HCT) in those who are appropriate candidates for this approach. The best induction regimen for PCL is not known and there is great variability in clinical practice. Newer agents that are being incorporated into frontline and salvage therapy for MM have also demonstrated activity in PCL such as Immunomodulatory agents and the use of bortezomib with different combinations. PMID:21295388

Albarracin, Flavio; Fonseca, Rafael

2011-05-01

142

Accumulation of cell wall-bound phenolic metabolites and their upliftment in hairy root cultures of tomato ( Lycopersicon esculentum Mill.)  

Microsoft Academic Search

Alkaline hydrolysis of cell wall material of tomato hairy roots yielded ferulic acid as the major phenolic compound. Other\\u000a phenolics were 4-hydroxybenzoic acid, vanillic acid, 4-hydroxybenzaldehyde, vanillin and 4-coumaric acid. The content of phenolics\\u000a was much higher at the early stage of hairy root growth. The ferulic acid content decreased up to 30 days and then sharply\\u000a increased to 360 ?g\\/g at

Sudhamoy Mandal; Adinpunya Mitra

2008-01-01

143

Biclonal primary plasma cell leukemia  

Microsoft Academic Search

Authors present a multiparameter pathological study in a case of rapid biclonal primary plasma cell leukemia. The immunohistochemical\\u000a data revealed aberrant phenotypes (monocyte, epithelial and T-cell) probably in connection with microenvironmental influences.\\u000a Biclonality can be attributed to class switching during malignant transformation. Static image cytometry showed aneuploidy.\\u000a The blasts of this process are active immunoregulatory cells.

Zoltán TÓth; József Sipos

1998-01-01

144

Natural IFN-alpha therapy in hairy-cell leukaemia (namalva-type IFN--Wellferon).  

PubMed

More than 50 patients with hairy-cell leukaemia have now been entered into the British Wellferon (IFN) study, at different centres under the coordination of the Wellcome Research Laboratories. While the treatment duration and dosage varied between patients, the initial dose was usually 3 megaunits daily by intramuscular or subcutaneous injection. Although flu-like symptoms and mild somnolence were commonly experienced side-effects; cessation of IFN treatment as a result of such effects was necessary in only three patients. All patients irrespective of previous treatment showed some response and a complete (less than 5% hairy cells, HCs) bone marrow response was observed in 17. The degree of response was related to the duration of therapy. Immunological markers showed that there was no apparent increase in natural killer (NK) cells and no return of normal B lymphocytes. Light-chain-restricted B cells became reduced in parallel with the disappearance of morphological HCs. Absolute numbers of T cells were reduced, Leu2a+ preferentially, resulting in an increase in helper/suppressor ratios. The ratios (saturation index, SI) of saturated to unsaturated 18 carbon fatty acids (C18FA) of erythrocyte or leukocyte membranes, while abnormal in untreated patients, approached normal levels during IFN therapy. It is concluded that prolonged alpha IFN therapy is highly effective in HCL. The mechanism of action of IFN remains unknown, but indirect surface-marker data favours a direct effect on HCs. PMID:3306138

Worman, C P; Nethersell, A B; Bottomley, J M; Apostolov, K; Barker, W; Cawley, J C

1987-07-15

145

A paraneoplastic membranoproliferative glomerulonephritis with isolated C3 deposits associated with hairy cell leukaemia.  

PubMed

We describe a 35-year-old woman who presented with proteinuria and microscopic haematuria. Blood tests revealed a low C3 complement level, with no evidence of cryoglobulin. Renal biopsy showed a Type 1 membranoproliferative glomerulonephritis (MPGN) with isolated C3 deposits on immunofluorescence study. Bone marrow aspirate, done for monocytopenia, was consistent with a diagnosis of hairy cell leukaemia (HCL). Both haematological and nephrological diseases completely responded to treatment with cladribine, strongly suggesting that the renal disease was a paraneoplastic syndrome. To our knowledge, this is the first report of a non-cryoglobulinaemic MPGN associated to HCL. PMID:20335271

Abboud, Imad; Galicier, Lionel; De Labarthe, Adrienne; Dossier, Antoine; Glotz, Denis; Verine, Jérôme

2010-06-01

146

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

PubMed Central

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

2014-01-01

147

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

PubMed

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

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

2003-02-01

148

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

149

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

150

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

151

Leukemia in donor cells after allogeneic hematopoietic stem cell transplant  

Microsoft Academic Search

The development of leukemia in donor cells after allogeneic hematopoietic stem cell transplant is an extremely rare event. We report here the case of a patient who developed myelodysplastic syndrome\\/acute myeloid leukemia, in cells of donor origin 3.5 years after related donor HSCT for refractory chronic lymphocytic leukemia and therapy-induced myelodysplastic syndrome. The origin of the leukemia was determined by

CG Brunstein; BA Hirsch; D Hammerschmidt; RC McGlennen; PL Nguyen; CM Verfaillie

2002-01-01

152

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

ClinicalTrials.gov

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

2011-12-09

153

Blinatumomab in Treating Younger Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia  

ClinicalTrials.gov

B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia

2014-05-19

154

Leukemia -- Chronic T-Cell Lymphocytic  

MedlinePLUS

... about 30% of people with LGLL also have rheumatoid arthritis (a chronic disease causing swelling in the joints of the hands, feet, wrists, knees, hips, or shoulders). T-cell prolymphocytic leukemia (T-PLL). T-PLL ...

155

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

2014-06-02

156

High density genome-wide DNA profiling reveals a remarkably stable profile in hairy cell leukaemia.  

PubMed

Hairy cell leukaemia (HCL) is a rare B-cell neoplasm for which the molecular mechanisms are largely unknown. High-density genome-wide DNA profiling was performed with Affymetrix 250K arrays to analyse copy number (CN) changes and loss of heterozygosity (LOH) in 16 cases of HCL. Four of 16 cases (25%) demonstrated gross non-recurrent CN deletions. Within the affected regions, we identified genes involved in bone marrow fibrosis (FGF12) and response to treatment (TP53) in individual cases. Large regions (> 5 Mb) of LOH without any concomitant DNA CN changes were identified in 5/16 (31%) HCL and were indicative of uniparental disomy UD. The germline origin of UD was demonstrated in one case for which a matched normal sample was available. Overall analysis of LOH showed that identical loci were recurrently targeted in chromosomes 1, 2 and 6. As a whole, however, HCL showed a remarkably stable genome. This finding adds to several other features that are unique to HCL among mature B-cell tumours. PMID:18397341

Forconi, Francesco; Poretti, Giulia; Kwee, Ivo; Sozzi, Elisa; Rossi, Davide; Rancoita, Paola M V; Capello, Daniela; Rinaldi, Andrea; Zucca, Emanuele; Raspadori, Donatella; Spina, Valeria; Lauria, Francesco; Gaidano, Gianluca; Bertoni, Francesco

2008-05-01

157

Phenotypic and functional characterization of the circulating NK compartment in hairy cell leukaemia.  

PubMed

A phenotypic and functional analysis of the circulating natural killer (NK) cell population was carried out in a series of patients with hairy cell leukaemia (HCL). The overall mean NK activity of both the mononuclear and T cell fractions was reduced compared to that of normal controls (466 lytic units (lu) v 573 lu and 226 lu v 381 lu, respectively), though this difference did not reach statistical significance (P less than 0.05). Individual analysis of the data showed that in five out of 15 and in seven out of 16 cases the K562 killing by the mononuclear and T cells respectively was below the lowest s.d. limit for normal subjects. This reduced NK function was associated with a decreased ability of the effector cells to bind the target. The NK response to exogenous human leucocyte interferon was also generally depressed in cases with a low basal NK activity. The functional studies were complemented with the evaluation of the membrane expression of NK associated antigens. The percentage of circulating T cells recognized by the monoclonal antibody (MoAb) Leu-7 was significantly higher (P less than 0.001) in HCL than in normal blood (25.2% +/- 10.2 v 11.9 +/- 5.9 s.d.). However, the reactivity with two other NK-related MoAb, Leu-11 and AB8.28, was significantly lower (7.1% +/- 6.9 and 9.8% +/- 8.5; P less than 0.002) than with Leu-7 and moderately reduced compared with that of normal circulating T cells (11.7% + 6.1 & 12% + 5.5). These findings suggest that in a proportion of patients with HCL there is an impairment of the NK compartment, which may contribute towards the occurrence of the infective complications which are the primary cause of death in this disease. PMID:3742880

Foa, R; Lauria, F; Lusso, P; Raspadori, D; Fierro, M T; Tazzari, P L; Caudana, L; Matera, L

1986-05-01

158

Phenotypic and functional characterization of the circulating NK compartment in hairy cell leukaemia.  

PubMed Central

A phenotypic and functional analysis of the circulating natural killer (NK) cell population was carried out in a series of patients with hairy cell leukaemia (HCL). The overall mean NK activity of both the mononuclear and T cell fractions was reduced compared to that of normal controls (466 lytic units (lu) v 573 lu and 226 lu v 381 lu, respectively), though this difference did not reach statistical significance (P less than 0.05). Individual analysis of the data showed that in five out of 15 and in seven out of 16 cases the K562 killing by the mononuclear and T cells respectively was below the lowest s.d. limit for normal subjects. This reduced NK function was associated with a decreased ability of the effector cells to bind the target. The NK response to exogenous human leucocyte interferon was also generally depressed in cases with a low basal NK activity. The functional studies were complemented with the evaluation of the membrane expression of NK associated antigens. The percentage of circulating T cells recognized by the monoclonal antibody (MoAb) Leu-7 was significantly higher (P less than 0.001) in HCL than in normal blood (25.2% +/- 10.2 v 11.9 +/- 5.9 s.d.). However, the reactivity with two other NK-related MoAb, Leu-11 and AB8.28, was significantly lower (7.1% +/- 6.9 and 9.8% +/- 8.5; P less than 0.002) than with Leu-7 and moderately reduced compared with that of normal circulating T cells (11.7% + 6.1 & 12% + 5.5). These findings suggest that in a proportion of patients with HCL there is an impairment of the NK compartment, which may contribute towards the occurrence of the infective complications which are the primary cause of death in this disease.

Foa, R; Lauria, F; Lusso, P; Raspadori, D; Fierro, M T; Tazzari, P L; Caudana, L; Matera, L

1986-01-01

159

711. Treatment of Acute Myeloid Leukemia by rAAV 8 Vector Mediated Human Interferon-? Gene Transfer  

Microsoft Academic Search

Alpha-interferons are widely used in the treatment of hematological malignancies such as CML, multiple myeloma and hairy cell leukemia. However their efficacy in the management of acute myeloid leukemia (AML) has not been fully evaluated. Furthermore the antitumour effects of the related ?-interferon have also not been systematically investigated in AML. Treatment with recombinant interferon is limited by its short

Reuben Benjamin; Andrew M. Davidoff; Pizzey Arnold; Nalini Singh; Asim Khwaja; Jenny McIntosh; Cathy C. Y. Ng; Tony Meager; Meenu Wadhwa; Amit C. Nathwani

2005-01-01

160

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

161

Cytoplasmic Fibrils in Plasma Cell Leukemia  

Microsoft Academic Search

In a patient with plasma cell leukemia, associated with pleural effusion, ultrastructural studies of the peripheral blood plasma cells showed an abundance of cytoplasmic fibrils. The nature of fibrils was not clarified, but they were not amyloid fibrils. This finding, coupled with a liaterature review, suggests that the cytoplasmic fibrils in plasma cells may be an additional cytological feature of

Makio Ogawa; Ronald A. Preston; Matthew D. Carson; Atsushi Komiyama; Samuel S. Spicer

1976-01-01

162

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.

Burch, Micah; Krause, John R.

2014-01-01

163

Adult T-cell leukemia/lymphoma.  

PubMed

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

Graham, Robbie L; Burch, Micah; Krause, John R

2014-07-01

164

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

165

Autofluorescence characteristics of human leukemia cells and mononuclear cells  

NASA Astrophysics Data System (ADS)

Autofluorescence spectroscopy is a powerful method to identify the endogenous fluorophores in normal and cancerous cells. The purpose of this study is to characterize the autofluorescence spectra of human normal and leukemia cells. Autofluorescence measurements of each cell line are performed over a wide range of cell concentrations. All of the leukemia cells indicate a statistically significant increase in the tryptophan fluorescence relative to that of the normal cells, while no statistically significant differences are observed in the reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) fluorescence between the normal and leukemia cells. The results suggest that the differences in autofluorescence spectra for leukemia cells and mononuclear cells may be attributed in part to differences in endogenous fluorophores of different cells.

Xiao, Lifu; Liao, Xiaoying; Lin, Lisheng; Huang, Huifang; Chen, Yuanzhong; Li, Buhong

2010-11-01

166

Plasma Cell Leukemia (PCL): A Report on 15 Patients  

Microsoft Academic Search

Fifteen patients presenting with plasma tients developed meningeal plasma cell cell leukemia (PCL) are reported in detail. leukemia and is reported in detail. Cyto- The clinicopathologic features of PCL differ morphologic assessment of PCL cells from typical myeloma and resemble those showed nuclear immaturity and obvious of acute leukemia: patients with PCL have nuclear\\/cytoplasmic asynchrony. Despite less bone disease but

R. K. Woodruff; J. S. Malpas; A. M. Paxton; T. A. Lister

1978-01-01

167

Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells  

Microsoft Academic Search

Aggressive natural killer-cell leukemia (ANKL) is a rare form of large granular lymphocyte leukemia, which is characterized by a systemic proliferation of NK cells. The clinical features of 22 ANKL cases were analyzed. Hepatomegaly (64%), splenomegaly (55%) and lymphadenopathy (41%) were also frequently observed. Leukemic cells were identified as CD1?, CD2+, surface CD3?, CD4?, CD5?, CD7+, CD8+\\/?, CD10?, CD11b+\\/?, CD13?,

R Suzuki; J Suzumiya; S Nakamura; S Aoki; A Notoya; S Ozaki; H Gondo; N Hino; H Mori; H Sugimori; K Kawa; K Oshimi

2004-01-01

168

Plasma cell leukemia: a rare condition  

Microsoft Academic Search

Plasma cell leukemia (PCL) is a rare lymphoproliferative disorder characterized by a malignant proliferation of plasma cells\\u000a in the bone marrow and peripheral blood. PCL is also characterized by a fulminant course and poor prognosis. Diagnosis of\\u000a PCL is established based on Kyle's criteria which include an absolute plasma cell number comprising greater than 20% of peripheral\\u000a blood cells. PCL

Víctor Hugo Jiménez-Zepeda; Virginia Jeanet Domínguez

2006-01-01

169

T-Cell Therapy of Leukemia  

Microsoft Academic Search

Background: The demonstration that immune-mediated elimination of leukemia contributes to the success of allogeneic hematopoietic stem cell transplantation (HSCT) has renewed interest in the development of immune-based therapies that might be used to augment the antileukemic effect of HSCT or in patients who are not receiving HSCT. Methods: The authors reviewed studies that have analyzed the mechanisms that may be

Stanley R. Riddell; Makoto Murata; Sophia Bryant; Edus H. Warren

2002-01-01

170

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

SciTech Connect

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

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

2009-09-04

171

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

172

Multiple transformation of plant cells by Agrobacterium may be responsible for the complex organization of T-DNA in crown gall and hairy root  

Microsoft Academic Search

Inoculation of carrot discs and Lotus corniculatus plantlets with mixtures of different Agrobacterium rhizogenes or of A. rhizogenes and A. tumefaciens or with Agrobacterium strains harboring both an Ri and a modified Ti plasmid resulted in frequent multiple (pluribacterial) transformation of cells, as revealed by the mixed opine-type of hairy roots arising from them. Multiple transformation may account for the

Annik Petit; André Berkaloff; Jacques Tempé

1986-01-01

173

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

174

Musashi1 and Hairy and Enhancer of Split 1 High Expression Cells Derived from Embryonic Stem Cells Enhance the Repair of Small-Intestinal Injury in the Mouse  

Microsoft Academic Search

Background  Embryonic stem cells have great plasticity. In this study, we repaired impaired small intestine by transplanting putative\\u000a intestinal epithelial stem cells (Musashi1 and hairy and enhancer of split 1 high expression cells) derived from embryonic\\u000a stem cells.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  The differentiation of definitive endoderm in embryoid bodies, derived from male ES-E14TG2a cells by the hanging-drop method,\\u000a was monitored to define a time

Tao YuShao-Yang; Shao-Yang Lan; Bin Wu; Qiu-Hui Pan; Liu Shi; Kai-Hong Huang; Ying Lin; Qi-Kui Chen

2011-01-01

175

Plasma cell leukemia: advantages of treatment with bortezomib  

Microsoft Academic Search

Plasma cell leukemia is an aggressive variant of multiple myeloma affecting 4% of all cases of the latter. It is characterized\\u000a by the presence of at least 20% plasma cells circulating in the peripheral blood, equivalent to an absolute number greater\\u000a than 2,000\\/mm3. Plasma cell leukemia exits in two forms: primary or de novo plasma cell leukemia (60%) and the

N. Fraimout; B. Kadouch; M. Ticchioni; N. Mounier

2008-01-01

176

Different Roles of the Mevalonate and Methylerythritol Phosphate Pathways in Cell Growth and Tanshinone Production of Salvia miltiorrhiza Hairy Roots  

PubMed Central

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.

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

2012-01-01

177

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.

178

Detection of Mutant p53 in Clam Leukemia Cells  

Microsoft Academic Search

Leukemia in the soft-shell clam,Mya arenaria,is characterized by tumor cells which are detected initially in the hemolymph. This disease is much more common in clams inhabiting polluted waters, suggesting an environmental component to its pathogenesis. In this study, leukemia cells were identified using a murine monoclonal antibody, 1E10, which recognizes a leukemia-specific protein expressed by tumor cells. Mutant p53 protein

Colin M. Barker; Richard J. Calvert; Charles W. Walker; Carol L. Reinisch

1997-01-01

179

Treatment of hairy cell leukaemia (HCL) with 2-chlorodeoxyadenosine (2-CdA): identification of parameters predictive of adverse effects.  

PubMed

2-chlorodeoxyadenosine (2-CdA) induces high complete remission (CR) rates in hairy cell leukaemia (HCL), but is associated with serious toxicities. Therefore we reviewed our experience with 2-CdA in 16 HCL patients, with special attention to adverse effects. One-third of patients presented severe neutropenic infections and/or required prolonged blood support. Patients with low tumour mass and moderate cytopenias were more likely to achieve CR, whereas those with high tumour burden and severe bone marrow impairment were at increased risk of severe infection and blood product requirements. All these unfavourable parameters may be corrected by short-term alpha-interferon (IFN) therapy. Therefore we suggest that patients with unfavourable presenting features might benefit from IFN therapy before 2-CdA. PMID:9359518

Legrand, O; Vekhoff, A; Marie, J P; Zittoun, R; Delmer, A

1997-10-01

180

Plasma cell leukemia producing monoclonal immunoglobulin E  

Microsoft Academic Search

A 78-year-old male with lumbar pain and dim consciousness presented the clinical pictures of plasma cell leukemia (PCL) producing\\u000a a large amount of monoclonal immunoglobulin E (IgE)\\/kappa protein. Laboratory investigation demonstrated an elevated serum\\u000a calcium level and renal dysfunction. Systemic bone X-ray survey disclosed only a solitary osteolytic lesion. Circulating plasma\\u000a cells demonstrated CD19?\\/CD56? and MPC-1?\\/CD49e?\\/CD45+\\/?, the latter indicating the

Yuzuru Takemura; Masanobu Ikeda; Kahori Kobayashi; Yuji Nakazawa; Yuichi Mori; Toshimi Mitsuishi; Hiroki Ishigame; Fumiko Kameko; Kiyotaka Fujita; Ryo Ichinohasama

2009-01-01

181

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

182

Laser activated nanothermolysis of leukemia cells monitored by photothermal microscopy  

NASA Astrophysics Data System (ADS)

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

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

2005-04-01

183

Prognostic significance of karyotypic abnormalities in B cell chronic lymphocytic leukemia: an update.  

PubMed

Cytogenetic analyses by G-banding and/or Q-banding techniques of leukemic B cells were performed in 102 patients with chronic lymphocytic leukemia (CLL), including six with prolymphocytic leukemia (PLL), one with hairy cell leukemia (HCL), and one with Waldenstrom's macroglobulinemia (WM) from 1979 through 1983. Follow-up after cytogenetic study ranged from 24 to 70 months. Seventeen patients had stage 0, 10 had stage I, 31 had stage II, and 44 had stage III or IV. Adequate metaphases were obtained for karyotypic analysis in 86 (84%) of 102 patients. Of these 86 patients with adequate metaphases, 43 had normal karyotypes (50%) and 43 had abnormal karyotypes (50%), of which trisomy 12 was the most frequent. Ten patients had trisomy 12 as the sole abnormality, 14 had trisomy 12 in combination with other abnormalities, and the remaining 19 had other abnormalities without trisomy 12. Abnormal karyotypes were more frequently associated with patients with advanced stages than those with early stages of the disease. Response rate to chemotherapy was significantly higher in patients with normal karyotypes than in those with abnormal karyotypes. Of eight patients who subsequently developed Richter's syndrome, seven initially had complex karyotypic changes with or without trisomy 12. These observations suggest that the chances of development of Richter's syndrome in CLL patients with multiple chromosome changes may be much higher than in those with either simple trisomy 12 or a normal karyotype. Mean frequency of abnormal metaphases was significantly higher in patients with complex trisomy 12 in combination with other changes than in those with trisomy 12 as the sole abnormality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3317853

Han, T; Henderson, E S; Emrich, L J; Sandberg, A A

1987-10-01

184

Adult T-cell leukemia-lymphoma.  

PubMed

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

Tsukasaki, Kunihiro

2012-04-01

185

Hyperviscosity Syndrome in a Patient with Plasma Cell Leukemia  

Microsoft Academic Search

A patient with plasma cell leukemia and IgG (K) M-component, who developed a hyperviscosity syndrome is reported. To our knowledge, this complication has not yet been reported in plasma cell leukemia.Copyright © 1979 S. Karger AG, Basel

Dan Douer; Avraham Weinbergerr; Meir Djaldetti; Jack Asherov; Israel Pick; Jack Pinkhas

1979-01-01

186

Leukemia-associated antigens are critical for the proliferation of acute myeloid leukemia cells.  

PubMed

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. With intensive induction therapy, most patients younger than 60 years achieve complete remission. However, even if these younger patients were treated intensively, more than 50% will relapse. Clinical results of patients older than 60 years are more unfavorable. Therefore, in all patients with AML, the overall survival is still low. In the past decade, several leukemia-associated antigens (LAA) have been identified in patients with acute myeloid leukemia. BAGE, BCL-2, OFA-iLRP, FLT3-ITD, G250, hTERT, PRAME, proteinase 3, RHAMM, survivin, and WT-1 are all LAAs that have been shown to induce CD8+ T-cell recognition and for some antigens also humoral immune responses. Interestingly, most of these LAAs are linked to cell cycle or proliferation. This article discusses the balance between LAA-driven leukemia cell expansion and the elimination of these cells through attacks on LAAs by the immune system. Current knowledge of the function and CD8+ T-cell recognition of LAAs is reviewed and an outlook is given on how to improve T-cell responses to LAAs in acute myeloid leukemia cells. PMID:19010831

Greiner, Jochen; Bullinger, Lars; Guinn, Barbara-ann; Döhner, Hartmut; Schmitt, Michael

2008-11-15

187

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.

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

2013-01-01

188

Comparison of growth properties of carrot hairy root in various bioreactors  

Microsoft Academic Search

Growth properties of carrot hairy root cells in various bioreactors were investigated. A turbine-blade reactor and an immobilized rotating drum reactor were found to be advantageous for the hairy root culture because of a high oxygen transfer coefficient (k in L a). After 30 days of culture, 10 g\\/l of dry hairy root cells were obtained in both bioreactors and

Osamu Kondo; Hiroyuki Honda; Masahito Taya; Takeshi Kobayashi

1989-01-01

189

Establishment and characterization of human B cell precursor-leukemia cell lines  

Microsoft Academic Search

A large number of continuous human leukemia cell lines have been established over the last three decades. Clearly, leukemia cell lines have become important research tools. Here, we have summarized the immunological, molecular and standard cytogenetic features of a panel of well characterized B cell precursor (BCP)-leukemia cell lines which were derived from patients with acute lymphoblastic\\/undifferentiated leukemia (ALL\\/AUL) or

Yoshinobu Matsuo; Hans G Drexler

1998-01-01

190

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.

2012-01-01

191

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

Federal Register 2010, 2011, 2012, 2013

...of Sciences (NAS) Institute of Medicine committee report, Veterans and...Exposure to Herbicides, Institute of Medicine (IOM) of the NAS, and other...According to Harrison's Principles of Internal Medicine (Harrison's Online,...

2010-03-25

192

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

Federal Register 2010, 2011, 2012, 2013

...infectious diseases associated with military service in the Southwest Asia...direct link to incurrence during military service. Consequently, VA...suggested that VA should guide the military services on presumptives related...there is a relationship between PTSD or stress and...

2010-08-31

193

Transgenic hairy roots  

Microsoft Academic Search

Agrobacterium rhizogenes causes hairy root disease in plants. The neoplastic roots produced by A. rhizogenes infection is characterized by high growth rate and genetic stability. These genetically transformed root cultures can produce higher levels of secondary metabolites or amounts comparable to that of intact plants. Hairy root cultures offer promise for production of valuable secondary metabolites in many plants. The

Archana Giri; M. Lakshmi Narasu

2000-01-01

194

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

2014-02-13

195

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

ClinicalTrials.gov

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

2013-07-01

196

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

197

Donor cell leukemia after bone marrow transplantation in the Friend leukemia in mice.  

PubMed

After lethal irradiation (800 R) Friend virus (FV-P)-infected leukemic DBA/2 mice were transplanted with normal bone marrow cells. Isogeneic transplantation led to an immediate relapse of leukemia. Therefore, allogeneic bone marrow cells were taken from almost FV-P resistant C57BL/6 mice. A measure of leukemia development was given by the number of erythropoietin-independent erythroid colonies (CFU-EI) in bone marrow and spleen, characteristic for the Friend leukemia. Even after allogeneic transplantation leukemia recurred after 5 to 19 days. By an electrophoretic analysis of the hemoglobin, it could be shown that the transformed erythropoiesis was donor derived. Thus, marrow of C57BL/6 origin loses its FV-P resistance in allogeneic leukemic lethally irradiated recipients and is transformed by the surviving virus. PMID:6986694

Kreja, L; Seidel, H J; Kohne, E

1980-02-01

198

Novel Therapeutic Targets for Ph+ Chromosome Leukemia and Its Leukemia Stem Cells: A Dissertation  

Microsoft Academic Search

The human Philadelphia chromosome (Ph) arises from a translocation between chromosomes 9 and 22 [t(9;22)(q34;q11)]. The resulting chimeric BCR-ABL oncogene encodes a constitutively activated, oncogenic tyrosine kinase that induces chronic myeloid leukemia (CML) and B-cell acute lymphoblastic leukemia (B-ALL). The BCR-ABL tyrosine kinase inhibitor (TKI), imatinib mesylate, induces a complete hematologic and cytogenetic response in the majority of CML patients,

Cong Peng

2010-01-01

199

Two Cases of Secondary Acute Myeloid Leukemia Accompanying Adult T-Cell Leukemia\\/Lymphoma  

Microsoft Academic Search

We identified 2 cases of secondary acute myeloid leukemia (AML) following adult T-cell leukemia\\/lymphoma (ATL) in patients\\u000a who had previously received chemotherapy. Both cases were thought to represent therapy-related AML because the patients had\\u000a previously received combination chemotherapy including epipodophyllotoxin, anthracycline, and alkylating agents for the ATL.\\u000a The cases were diagnosed as AML M4 with eosinophilia and AML M2, with

Satsuki Owatari; Maki Otsuka; Kimiharu Uozumi; Taketsugu Takeshita; Shuichi Hanada

2007-01-01

200

Leukemia  

MedlinePLUS

... leukemias. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: Elsevier Saunders; 2011: ... leukemias. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: Elsevier Saunders; 2011: ...

201

Pentostatin (Nipent) in T-cell malignancies. Leukemia Cooperative Group and the European Organization for Research and Treatment of Cancer.  

PubMed

Within this phase II trial of the European Organization for Research and Treatment of Cancer, we have investigated the safety and efficacy of pentostatin (Nipent; SuperGen, San Ramon, CA) in refractory lymphoid malignancies. Pentostatin was administered at a dosage of 4 mg/m2 every week for the first 3 weeks, then every 14 days, followed by maintenance therapy of 4 mg/m2 monthly for a maximum of 6 months. We have previously reported the results in T- and B-cell prolymphocytic leukemia, B-cell chronic lymphocytic leukemia, and hairy cell leukemia This report focuses on the outcome in T-cell malignancies: T-cell chronic lymphocytic leukemia, Sézary syndrome, mycosis fungoides, and T-zone lymphoma. Of 92 patients with these diagnoses enrolled, 76 were evaluable for response and toxicity, ie, 25 of 28 with T-cell chronic lymphocytic leukemia, 21 of 26 with Sézary syndrome, 22 of 26 with mycosis fungoides, and eight of 12 with T-zone lymphoma. All patients had progressive and advanced disease. Sixteen patients (21%) died during the first 9 weeks of treatment: 12 of progressive disease, two of infectious complications thought to be unrelated to treatment, one of myocardial infarction, and one of renal failure related to administration of intravenous contrast. Major toxicity (grades 3 and 4) included infection in 10.5% of patients, nausea/vomiting in 5%, and hepatotoxicity in 3%. One patient (1.3%) achieved a complete remission and 15 (19.7%) a partial remission. Better results were achieved in patients with Sézary syndrome or mycosis fungoides (complete remission + partial remission = 33.4% and 22.7%, respectively) than in patients with T-cell chronic lymphocytic leukemia (8%) or T-zone lymphoma (25%). We conclude that pentostatin is active in low-grade T-cell malignancies. Toxicities are mild to moderate at the dose schedule administered. Severe hematologic toxicity has not been observed. The efficacy at the present dose level is moderate. A higher dose might be necessary for some T-cell malignancies. PMID:10877053

Ho, A D; Suciu, S; Stryckmans, P; De Cataldo, F; Willemze, R; Thaler, J; Peetermans, M; Döhner, H; Solbu, G; Dardenne, M; Zittoun, R

2000-04-01

202

Gene expression profiling in T-cell acute lymphoblastic leukemia  

Microsoft Academic Search

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

Adolfo A Ferrando; A. Thomas Look

2003-01-01

203

Peripheral blood 8 colour flow cytometry monitoring of hairy cell leukaemia allows detection of high-risk patients.  

PubMed

Although purine analogues have significantly improved the outcome of hairy cell leukaemia (HCL) patients, 30-40% relapse, illustrating the need for minimal residual disease (MRD) markers that can aid personalized therapeutic management. Diagnostic samples from 34 HCL patients were used to design an 8-colour flow cytometry (8-FC) tube for blood MRD (B/RD) analysis (188 samples) which was compared to quantitative IGH polymerase chain reaction (Q-PCR) on 83 samples and to qualitative consensus IGH PCR clonality analysis on 165 samples. Despite heterogeneous HCL phenotypes at diagnosis, discrimination from normal B lymphocytes was possible in all cases using a single 8-FC tube, with a robust sensitivity of detection of 10(-4) , comparable to Q-PCR at this level, but preferable in terms of informativeness, simplicity and cost. B/RD assessment of 15 patients achieving haematological complete remission after purine analogues was predictive of a clinically significant relapse risk: with a median follow-up of 95 months; only one of the nine patients with reproducible 8-FC B/RD levels below 10(-4) (B/RD(neg) ) relapsed, compared to 5/6 in the B/RD(pos) group (P = 0·003). These data demonstrate the clinical interest of a robust 8-FC HCL B/RD strategy that could become a surrogate biomarker for therapeutic stratification and new drug assessment, which should be evaluated prospectively. PMID:24661013

Garnache Ottou, Francine; Chandesris, Marie-Olivia; Lhermitte, Ludovic; Callens, Céline; Beldjord, Kheira; Garrido, Marlene; Bedin, Anne-Sophie; Brouzes, Chantal; Villemant, Sarah; Rubio, Marie-Thérèse; Belanger, Coralie; Suarez, Felipe; Deau, Bénédicte; Lefrère, François; Hermine, Olivier; Asnafi, Vahid; Varet, Bruno; Macintyre, Elizabeth

2014-07-01

204

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

PubMed

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

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

2014-06-01

205

Laser nanothermolysis of human leukemia cells using functionalized plasmonic nanoparticles  

PubMed Central

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

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

2012-01-01

206

[Adult T cell leukemia-lymphoma (ATL)].  

PubMed

Adult T-cell leukemia-lymphoma(ATL) is a distinct malignancy of CD4+/CD25+/ CCR4+/FoxP3+ or - Treg/TH2 cells etiologically associated with human T-cell lymphotropic virus type I (HTLV-1). ATL is a single HTLV-1 disease entity with diverse molecular features. Also, the clinical features and prognosis are diverse leading to subtype-classification into acute, lymphoma, chronic, and smoldering types defined by organ involvement, and LDH and calcium values. In case acute, lymphoma or unfavorable chronic subtypes (aggressive ATL), and favorable chronic or smoldering ATL (indolent ATL), intensive chemotherapy followed by allo-HSCT and watchful waiting until disease progression has been recommended, respectively in Japan. Several new agent-trials for ATL are ongoing and in preparation, including a defucosylated humanized anti-CC chemokine receptor 4 monoclonal antibody, IL2-fused with diphtheria toxin, histone deacetylase inhibitors, a purine nucleoside phosphorylase inhibitor, a proteasome inhibitor and lenalidomide. PMID:24724415

Tsukasaki, Kunihiro

2014-03-01

207

Early T-cell precursor leukemia: a subtype of high risk childhood acute lymphoblastic leukemia.  

PubMed

Acute lymphoblastic leukemia includes T-cell acute lymphoblastic leukemia (T-ALL) and B-cell acute lymphoblastic leukemia (B-ALL). In children, T-ALL usually has a worse prognosis than B-ALL, although childhood T-ALL prognoses have improved remarkably. The varying outcomes among T-ALL cases suggest that an unrecognized biological heterogeneity may contribute to chemo-resistance. Deep exploration of T-lymphocyte development in recent years has found a subgroup of patients with a phenotype that resembles early T-cell precursor, which confers a much poorer prognosis than any other form of T-ALL. This novel subtype of T-ALL was called early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Flow cytometry data from T-ALL patients enrolled in Shanghai Children's Medical Center between July 2002 and October 2010 were assessed according to Dr. Campana's protocol. Among total 89 T-ALL cases, 74 cases had enough immunophenotype data available to differentiate between ETP (CD1a(-), CD8(-), CD5(dim), at least one marker of stem cell or myeloid lineage) and non-ETP. From these 74 subjects, 12 ETP-ALL cases (16.2%) were identified. The event-free survival (EFS) rate at 66.8 months was 11.1% ± 10.1% for ETP-ALL and 57.6% ± 5.6% for non-ETP-ALL (P = 0.003). The overall survival rates were 13.3% ± 11.0% for ETP-ALL and 64.7% ± 6.3% for non-ETP-ALL (P = 0.002). Our findings demonstrate that early T-cell precursor leukemia is a very high-risk subtype of acute lymphoblastic leukemia with poor prognosis. PMID:23065427

Ma, Meilin; Wang, Xiang; Tang, Jingyan; Xue, Huiliang; Chen, Jing; Pan, Ci; Jiang, Hua; Shen, Shuhong

2012-12-01

208

Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells.  

PubMed

Aggressive natural killer-cell leukemia (ANKL) is a rare form of large granular lymphocyte leukemia, which is characterized by a systemic proliferation of NK cells. The clinical features of 22 ANKL cases were analyzed. Hepatomegaly (64%), splenomegaly (55%) and lymphadenopathy (41%) were also frequently observed. Leukemic cells were identified as CD1-, CD2+, surface CD3-, CD4-, CD5-, CD7+, CD8+/-, CD10-, CD11b+/-, CD13-, CD16+, CD19-, CD20-, CD25-, CD33(-), CD34-, CD38+, CD56+, CD122+, HLA-DR+ and TCR-. Two of the 16 cases examined for CD57 were positive and three of the seven cases examined for cytoplasmic CD3. Epstein-Barr virus was detected in the tumor cells of 11 of the 13 cases examined. No common cytogenetic abnormalities were identified and 6q anomaly was detected in only one. Three of 13 patients treated with chemotherapy containing anthracycline/anthraquinone attained complete remission, in contrast to none of the eight who were treated with regimens without anthracycline. Although the overall prognosis was poor with a median survival of 58 days, those who attained remission showed better prognosis (P=0.005). These findings suggest that ANKL is an entity of mature cytotoxic NK-cell neoplasms with distinct phenotype and disease presentations. Intensive treatment for ANKL may result in a better prognosis. PMID:14961041

Suzuki, R; Suzumiya, J; Nakamura, S; Aoki, S; Notoya, A; Ozaki, S; Gondo, H; Hino, N; Mori, H; Sugimori, H; Kawa, K; Oshimi, K

2004-04-01

209

FBXW7 mutation in adult T-cell and B-cell acute lymphocytic leukemias.  

PubMed

The FBXW7 (also known as AGO, hCDC4, FBW7 and SEL-10) gene encodes a subunit of an ubiquitin protein ligase which regulates levels of cyclin E, NOTCH and other proteins. Engineered FBXW7 null cells display cell cycle and chromosome stability defects. Mutations of FBXW7 have been found in human colorectal, ovarian, endometrial tumors and T-cell acute lymphocytic leukemias. Prompted by these findings we have examined acute myeloid leukemia, non-Hodgkin's lymphoma, T-cell acute lymphocytic leukemia, B-cell acute lymphocytic leukemia and adult T-cell leukemia DNA for mutations of the FBXW7 gene. Mutations were detected by PCR-SSCP of all coding exons of the three isoforms of FBXW7, shifted bands were direct sequenced. As expected, mutations were found in T-cell acute lymphocytic leukemias. However mutations of FBXW7 were also found in four of 118 B-cell acute lymphocytic leukemias and one of 24 adult T-cell leukemia samples. The nucleotide changes consisted of an insertion, resulting in a frameshift mutation, and missense mutations of highly conserved residues. All mutations affected the FBXW7 target interacting domain. These observations suggest that disruption of FBXW7 has a role in several forms of lymphocytic leukemias and not exclusively T-cell acute lymphocytic leukemia. PMID:18485478

Song, Jee Hoon; Schnittke, Nikolai; Zaat, April; Walsh, Christine S; Miller, Carl W

2008-11-01

210

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

ClinicalTrials.gov

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 Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

2014-06-30

211

Transmission and scanning electron microscopy study on plasma cell leukemia  

Microsoft Academic Search

Summary The peripheral blood cells of a patient with acute plasma cell leukemia were examined with transmission (TEM) and scanning (SEM) electron microscopes. The TEM features of the immature plasma cells comprised lobulated and irregulary shaped nuclei, with scanty heterochromating and bizarre nucleoli, parallel arrays of endoplasmic reticulum, cytoplasmic fibrils and numerous polymorphic mitochondria. SEM examination of the cells showed

B. Klein; U. Lewinski; F. Shabtai; N. Freidin; M. Djaldetti

1977-01-01

212

Adhesion-induced drug resistance in leukemia stem cells.  

PubMed

The co-culture of TF-1 leukemia cells and MS-5 stromal cells produces a cobblestone area which partially mimics the leukemia stem cell niche. The adhering leukemia cells are shown to become less sensitive to cytarabine, etoposide and daunorubicin. These changes are associated with an increased proportion of the G0/G1 phase, increased upregulation of cyclin-dependent kinase inhibitors, and increased levels of Bcl-2, but not with any change in the expression of BAX or drug transporters such as ABCG2 and MDR1, compared to monocultured leukemic cells. In addition, we demonstrate using a bioimaging technique that daunorubicin accumulates in the lysosomes of the adherent leukemic cells and that V-ATPase is activated. These findings suggest that adhesion alone can lead to drug resistance in leukemic stem cells by various mechanisms. PMID:20689339

Funayama, Keiji; Murai, Fumihiko; Shimane, Miyuki; Nomura, Hitoshi; Asano, Shigetaka

2010-01-01

213

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

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; Juvenile Myelomonocytic 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; 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

2014-05-19

214

Hairy Transcriptional Repression Targets and Cofactor Recruitment in Drosophila  

PubMed Central

Members of the widely conserved Hairy/Enhancer of split family of basic Helix-Loop-Helix repressors are essential for proper Drosophila and vertebrate development and are misregulated in many cancers. While a major step forward in understanding the molecular mechanism(s) surrounding Hairy-mediated repression was made with the identification of Groucho, Drosophila C-terminal binding protein (dCtBP), and Drosophila silent information regulator 2 (dSir2) as Hairy transcriptional cofactors, the identity of Hairy target genes and the rules governing cofactor recruitment are relatively unknown. We have used the chromatin profiling method DamID to perform a global and systematic search for direct transcriptional targets for Drosophila Hairy and the genomic recruitment sites for three of its cofactors: Groucho, dCtBP, and dSir2. Each of the proteins was tethered to Escherichia coli DNA adenine methyltransferase, permitting methylation proximal to in vivo binding sites in both Drosophila Kc cells and early embryos. This approach identified 40 novel genomic targets for Hairy in Kc cells, as well as 155 loci recruiting Groucho, 107 loci recruiting dSir2, and wide genomic binding of dCtBP to 496 loci. We also adapted DamID profiling such that we could use tightly gated collections of embryos (2–6 h) and found 20 Hairy targets related to early embryogenesis. As expected of direct targets, all of the putative Hairy target genes tested show Hairy-dependent expression and have conserved consensus C-box–containing sequences that are directly bound by Hairy in vitro. The distribution of Hairy targets in both the Kc cell and embryo DamID experiments corresponds to Hairy binding sites in vivo on polytene chromosomes. Similarly, the distributions of loci recruiting each of Hairy's cofactors are detected as cofactor binding sites in vivo on polytene chromosomes. We have identified 59 putative transcriptional targets of Hairy. In addition to finding putative targets for Hairy in segmentation, we find groups of targets suggesting roles for Hairy in cell cycle, cell growth, and morphogenesis, processes that must be coordinately regulated with pattern formation. Examining the recruitment of Hairy's three characterized cofactors to their putative target genes revealed that cofactor recruitment is context-dependent. While Groucho is frequently considered to be the primary Hairy cofactor, we find here that it is associated with only a minority of Hairy targets. The majority of Hairy targets are associated with the presence of a combination of dCtBP and dSir2. Thus, the DamID chromatin profiling technique provides a systematic means of identifying transcriptional target genes and of obtaining a global view of cofactor recruitment requirements during development.

Bianchi-Frias, Daniella; Orian, Amir; Delrow, Jeffrey J; Vazquez, Julio; Rosales-Nieves, Alicia E

2004-01-01

215

Detection and characterization of human high molecular weight B cell growth factor receptors on leukemic B cells in chronic lymphocytic leukemia.  

PubMed Central

Human high molecular weight-B cell growth factor (HMW-BCGF) (60 kD) stimulates activated normal B cells, B cell precursor acute lymphoblastic leukemia (BCP-ALL) cells, hairy cell leukemia (HCL) cells, prolymphocytic leukemia (PLL) cells, and chronic lymphocytic leukemia (CLL) cells. The expression of human high molecular weight B cell growth factor (HMW-BCGF) receptors (R) on clonal populations of leukemic B cells in CLL was studied by ligand binding assays using 125I-labeled HMW-BCGF as well as by immunofluorescence/flow cytometry and Scatchard analyses using an anti-HMW-BCGF R monoclonal antibody (MAb), designated BA-5. There was a high correlation between HMW-BCGF R expression and responsiveness to HMW-BCGF. 60% of CLL cases constitutively expressed HMW-BCGF R and showed a marked proliferative response to HMW-BCGF in [3H]TdR incorporation assays as well as colony assays. Similarly, HCL cells, PLL cells, and activated normal B cells expressed functional HMW-BCGF R, as determined by ligand binding assays using 125I-HMW-BCGF, [3H]TdR incorporation assays, and reactivity with BA-5 MAb. Scatchard analyses indicated the existence of approximately 3,000 HMW-BCGF R/cell on HMW-BCGF responsive CLL cells with an apparent Ka value of 4.6 X 10(7) M-1. The concentrations of HMW-BCGF required for maximum stimulation of CLL cells were two to three orders of magnitude lower than those needed for half maximal receptor occupancy, indicating that only a small fraction of HMW-BCGF R need to be occupied to stimulate leukemic CLL B cells. Crosslinking of surface bound 125I-HMW-BCGF (60 kD) with the bivalent crosslinker DTSSP to its binding site on fresh CLL cells identified a 150-kD HMW-BCGF/HMW-BCGF R complex, suggesting an apparent molecular weight of 90 kD for the receptor protein. The growth stimulatory effects of HMW-BCGF on clonogenic CLL cells did not depend on accessory cells or costimulant factors. The anti-HMW-BCGF R monoclonal antibody BA-5 disrupted HMW-BCGF/HMW-BCGF R interactions at the level of clonogenic CLL cells and inhibited HMW-BCGF-stimulated CLL colony formation in vitro. To our knowledge, this study represents the first detailed analysis of expression, function, and structure of HMW-BCGF R on B lineage CLL cells. Images

Uckun, F M; Fauci, A S; Chandan-Langlie, M; Myers, D E; Ambrus, J L

1989-01-01

216

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

217

Leukemia stem cells in 2010: Current understanding and future directions  

Microsoft Academic Search

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

Michael W. Becker; Craig T. Jordan

2011-01-01

218

ETV6 mutations in early immature human T cell leukemias  

PubMed Central

Early immature T cell acute lymphoblastic leukemias (T-ALLs) account for ?5–10% of pediatric T-ALLs and are associated with poor prognosis. However, the genetic defects that drive the biology of these tumors remain largely unknown. In this study, analysis of microarray gene expression signatures in adult T-ALL demonstrated a high prevalence of early immature leukemias and revealed a close relationship between these tumors and myeloid leukemias. Many adult immature T-ALLs harbored mutations in myeloid-specific oncogenes and tumor suppressors including IDH1, IDH2, DNMT3A, FLT3, and NRAS. Moreover, we identified ETV6 mutations as a novel genetic lesion uniquely present in immature adult T-ALL. Our results demonstrate that early immature adult T-ALL represents a heterogeneous category of leukemias characterized by the presence of overlapping myeloid and T-ALL characteristics, and highlight the potential role of ETV6 mutations in these tumors.

Van Vlierberghe, Pieter; Ambesi-Impiombato, Alberto; Perez-Garcia, Arianne; Haydu, J. Erika; Rigo, Isaura; Hadler, Michael; Tosello, Valeria; Della Gatta, Giusy; Paietta, Elisabeth; Racevskis, Janis; Wiernik, Peter H.; Luger, Selina M.; Rowe, Jacob M.; Rue, Montserrat

2011-01-01

219

Leukomogenic factors downregulate heparanase expression in acute myeloid leukemia cells  

SciTech Connect

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

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

2005-10-07

220

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

221

Plant Cell and Hairy Root Cultures in Bioreactor-Based Production Processes.  

National Technical Information Service (NTIS)

Plant cell culture technology has progressed rapidly during recent decades to the point where a number of process systems have achieved or are approaching commercial operation. The aim of the work was to develop laboratory scale bietechnical production pr...

A. M. Nuutila

1994-01-01

222

Utilization of Catharanthus Roseus Hairy Root and Cell Suspension Cultures in Plant Biotechnology.  

National Technical Information Service (NTIS)

Plant cell culture technology finds increasing use in agricultural crop improvement, germplasm storage and commercial micropropagation as well as in fundamental studies of plant biochemistry, physiology and genetics. The production of useful chemicals by ...

L. Toivonen

1992-01-01

223

Novel non-viral method for transfection of primary leukemia cells and cell lines.  

PubMed

BACKGROUND: Tumor cells such as leukemia and lymphoma cells are possible targets for gene therapy. However, previously leukemia and lymphoma cells have been demonstrated to be resistant to most of non-viral gene transfer methods. METHODS: The aim of this study was to analyze various methods for transfection of primary leukemia cells and leukemia cell lines and to improve the efficiency of gene delivery. Here, we evaluated a novel electroporation based technique called nucleofection. This novel technique uses a combination of special electrical parameters and specific solutions to deliver the DNA directly to the cell nucleus under mild conditions. RESULTS: Using this technique for gene transfer up to 75% of primary cells derived from three acute myeloid leukemia (AML) patients and K562 cells were transfected with the green flourescent protein (GFP) reporter gene with low cytotoxicity. In addition, 49(+/- 9.7%) of HL60 leukemia cells showed expression of GFP. CONCLUSION: The non-viral transfection method described here may have an impact on the use of primary leukemia cells and leukemia cell lines in cancer gene therapy. PMID:14715084

Schakowski, Frank; Buttgereit, Peter; Mazur, Martin; Märten, Angela; Schöttker, Björn; Gorschlüter, Marcus; Schmidt-Wolf, Ingo GH

2004-01-12

224

Chaperone Rich Cell Lysate (CRCL) Vaccine for Chronic Myelogenous Leukemia.  

National Technical Information Service (NTIS)

We evaluated whether immunization of mice with dendritic cells (DCs) loaded with 12B1 murine bcr-abl+ leukemia -derived chaperone-rich cell lysates (CRCL) induced BCR-ABL specific immune responses in vivo. We found that splenocytes from mice immunized wit...

E. Katsanis

2004-01-01

225

Thalidomide Administration for the Treatment of Resistant Plasma Cell Leukemia  

Microsoft Academic Search

Plasma cell leukemia (PCL) is a rare plasma cell dyscrasia which may arise de novo or during the course of multiple myeloma (MM) and is then referred to as secondary PCL. Primary and secondary PCL occur in 1.6% of all MM cases. Both types of PCL are resistant to various treatment options similar to those administered to MM patients. Given

Stavroula Tsiara; Aristeidis Chaidos; Helen Kapsali; Evagelia Tzouvara; Konstantinos L. Bourantas

2003-01-01

226

Primary plasma cell leukemia followed by testicular plasmacytoma  

Microsoft Academic Search

Plasma cell leukemia (PCL) is a highly aggressive plasma cell disease characterized by a poor prognosis and a low response\\u000a rate to conventional therapy. Herein, we describe a 69-year-old patient with primary PCL, developing testicular disease while\\u000a in complete hematological remission, following by muscle involvement and peritoneal dissemination.

Caterina Giovanna Valentini; Valentina Bozzoli; Luana Fianchi; Maria Teresa Voso; Gianluigi Di Paolantonio; Marianna Criscuolo; Giuseppe Leone; Luigi Maria Larocca; Livio Pagano

2011-01-01

227

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

PubMed

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

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

2014-06-30

228

Reversal of drug resistance by silencing Survivin gene expression in acute myeloid leukemia cells  

Microsoft Academic Search

The role of Survivin in the pathogenesis of leukemia was explored in order to discover the ef- fective avenues for gene therapy. Most primary leukemia cells isolated from patients as well as three leukemia cell lines (HL-60, K562, and U937) all expressed Survivin gene. To investigate the relationship between Survivin and chemotherapeutic resistance, HL-60 cells were treated with daunorubicin (DNR),

Yao-Hui Wu; Zhi-Chao Chen; Ping Zou

2008-01-01

229

Incomplete Chromatin Condensation in Enlarged Rat Myelocytic Leukemia Cells  

PubMed Central

The distinguishable morphologic features of nuclei of acute myelogenous leukemia cells with enlarged size and finely distributed nuclear chromatin indicate incomplete chromosome condensation that can be related to elevated gene expression. To confirm this, interphase chromosome structures were studied in exponentially growing rat myelomonocytic leukemia 1 cells isolated at the University of Debrecen (My1/De cells). This cell line was established from primary rat leukemia chemically induced by 7,12-dimethylbenz[a]anthracene treatment. The enlarged nuclei of My1/De cells allowed improved fluorescent visualization of chromosomal structures. Increased resolution revealed major interphase intermediates consisting of (1) veil-like chromatin, (2) chromatin ribbon, (3) chromatin funnel, (4) chromatin bodies, (5) elongated prechromosomes, (6) seal-ring, spiral shaped, and circular chromosomal subunits, (7) elongated, bent, u- and v-shaped prechromosomes, and (8) metaphase chromosomes. Results confirmed the existence of the chromatin funnel, the first visible interphase chromosome generated by the supercoiling of the chromatin ribbon. Other intermediates not seen previously included the spiral subunits that are involved in the chromonemic folding of metaphase chromosomes. The existence of spiral subunits favors the helical coil model of chromosome condensation. Incomplete chromatin condensation in leukemia cells throughout the cell cycle is an indication of euchromatization contributing to enhanced gene expression and is regarded as a leukemic factor.

Trencsenyi, Gyorgy; Nagy, Gabor; Bako, Fruzsina; Kertai, Pal

2012-01-01

230

Proliferating cell nuclear antigen expression in childhood acute leukemia.  

PubMed

Proliferating cell nuclear antigen (PCNA) is a 36-Kd nuclear protein, identified as the auxiliary protein of DNA polymerase delta, that is upregulated in activated proliferating cells from a variety of tissues and species, including human lymphocytes. We have examined by two-dimensional polyacrylamide gel electrophoresis the expression of PCNA in various subtypes of childhood acute leukemia and have found differences in its expression according to subtype. These differences were not related to the initial peripheral white blood count, age, or sex, and appeared to reflect differences in proliferative activity between subtypes of acute leukemia. PMID:1975505

Keim, D; Hailat, N; Hodge, D; Hanash, S M

1990-09-01

231

Adult T-cell leukemia\\/lymphoma and HTLV1  

Microsoft Academic Search

Human T-cell leukemia\\/lymphoma virus type 1 (HTLV-1) was the first oncogenic human retrovirus to be discovered, more than\\u000a 25 years ago. HTLV-1 infects 15 to 20 million individuals worldwide. This oncoretrovirus can be transmitted in three ways:\\u000a horizontally (sexually), vertically (mother to child), and via blood transfusion. HTLV-1 causes two major diseases: adult\\u000a T-cell leukemia\\/lymphoma (ATLL) and tropical spastic paraparesis\\/HTLV-1-associated

Renaud Mahieux; Antoine Gessain

2007-01-01

232

[Secondary plasma cell leukemia. Report of 2 cases].  

PubMed

Plasma cell leukemia is considered as the leukemic variant of multiple myeloma. It is a rare entity. There are two forms: a secondary one following a known myeloma, the diagnosis of which is easy, and a primary one arising without a preceding phase of multiple myeloma. The diagnosis of the latter form is more difficult, a differential diagnosis has often to be discussed with other lymphoproliferative diseases. Prognosis is poor. We report 2 cases of secondary plasma cell leukemia diagnosed over ten years, among 59 of multiple myeloma cases. We describe the epidemiologic, clinical, biological and evolutionary characteristics. PMID:16220704

Sondes, Mseddi; Choumous, Kallel; Moez, Elloumi; Naourez, Ajmi; Fatma, Ben Said; Faiza, Makni; Taoufik, Souissi

2005-07-01

233

Amplification of IGH\\/CCND1 fusion gene in a primary plasma cell leukemia case  

Microsoft Academic Search

The IGH\\/CCND1 fusion gene has been reported in many hematologic tumors such as mantle cell lymphoma, chronic lymphocytic leukemia, prolymphocytic leukemia, multiple myeloma, and plasma cell leukemia. We report a case of plasma cell leukemia showing five IGH\\/CCND1 fusion signals by interphase fluorescence in situ hybridization (FISH). Conventional cytogenetic analysis and multicolor spectral karyotyping showed a complex karyotype that did

Tomohiro Ishigaki; Kouji Sasaki; Ken Watanabe; Norihiko Nakamura; Shigeo Toyota; Hirofumi Kobayashi; Shuji Tohda

2010-01-01

234

Elevated serum-soluble interleukin-2 receptor levels in patients with anaplastic large cell lymphoma  

Microsoft Academic Search

Levels of serum soluble interleukin 2 re- ceptor (sIL-2R) provide a reliable marker of disease activity in patients with hairy cell leukemia and adult T-cell leukemia\\/ lymphoma. The malignant cells in pa- tients with anaplastic large cell lym- phoma (ALCL) express CD30 and are usually positive for expression of CD25. We measured serum sIL-2R and soluble CD30 (sCD30) levels in

John E. Janik; John C. Morris; Stefania Pittaluga; Kristin McDonald; Mark Raffeld; Elaine S. Jaffe; Nicole Grant; Martin Gutierrez; Thomas A. Waldmann; Wyndham H. Wilson

235

Rotating hairy black holes.  

PubMed

We construct stationary black-hole solutions in SU(2) Einstein-Yang-Mills theory which carry angular momentum and electric charge. Possessing nontrivial non-Abelian magnetic fields outside their regular event horizon, they represent nonperturbative rotating hairy black holes. PMID:11329304

Kleihaus, B; Kunz, J

2001-04-23

236

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

237

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

2014-01-30

238

Stochastic acquisition of a stem cell-like state and drug tolerance in leukemia cells stressed by radiation  

Microsoft Academic Search

A rare population of leukemia cells have the properties of leukemia stem cells (LSCs) and cause resistance to therapy, but\\u000a their development is not clearly understood. In the current study, we show that a higher resistance to cytotoxic drug (Ara-C)\\u000a can be developed in the subpopulation of promyelocytic leukemia cells that survived radiation treatment. These drug-tolerant\\u000a leukemia cells (DTLs) are

Ga-Young Lee; Jae-Seung Shim; Bin Cho; Joo-Young Jung; Dong-Soon Lee; Il-Hoan Oh

2011-01-01

239

Copper ions regulate cytotoxicity of disulfiram to myeloid leukemia cells.  

PubMed

White blood cell (WBC) count is considered a prognostic risk factor in acute myeloid leukemia. As density of leukemic cells increases, the cytotoxic activity of certain anticancer drugs, such as vincristine and doxorubicin, progressively decreases. In this study, we investigated the cell density-dependent induction of apoptosis of human acute myeloid leukemia U937 and ML-1 cells by disulfiram (DSF), the dithiocarbamate drug recently proposed for treatment of human cancers. This effect is dependent on uptake of extracellular copper and its intracellular accumulation. High-density cells cannot uptake and accumulate this metal to a sufficient level that would allow induction of apoptosis due to progressive decrease of its extracellular concentration. Simple addition of copper can resume sensitivity of high-density leukemic cells to DSF and improve efficiency of anti-leukemic therapies using this drug, thus providing benefit to patients with high WBC count. PMID:19787200

Navrátilová, Jarmila; Jungová, Pavla; Vanhara, Petr; Preisler, Jan; Kanicky, Viktor; Smarda, Jan

2009-11-01

240

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.

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

241

Identification of cancer stem cells: from leukemia to solid cancers  

Microsoft Academic Search

Cancer stem cells (CSCs) are widely considered to be a small cell population in leukemia and many solid cancers with the properties\\u000a including self-renewal and differentiation to non-tumorigenic cancer cells. Identification and isolation of CSCs significantly\\u000a depend on the special surface markers of CSCs. Aberrant gene expression and signal transduction contribute to malignancies\\u000a of CSCs, which result in cancer initiation,

Yinghui Huang; Xiaoxue Qiu; Ji-Long Chen

2010-01-01

242

Molecular cytogenetic analysis of B-cell chronic lymphocytic leukemia  

Microsoft Academic Search

The genetic alterations underlying the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) are difficult to assess.\\u000a Cytogenetic studies are hindered by the low in vitro mitotic activity of the tumor cells and the limited resolution of chromosome\\u000a banding. Molecular genetic analyses are hampered by nonclonal cells contained in the specimens and by the limited knowledge\\u000a of candidate genes involved. As

S. Stilgenbauer; K. Döhner; M. Bentz; P. Lichter; H. Döhner

1998-01-01

243

Monoclonal B-Cell Lymphocytosis and Chronic Lymphocytic Leukemia  

Microsoft Academic Search

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

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

2008-01-01

244

Surface Markers on Leukemia and Lymphoma Cells: Recent Advances  

Microsoft Academic Search

Recent advances in immunology have led to important insights into leukocyte differentiation and the cellular on- gin of leukemia. It is now possible to precisely define stages of human lymphocyte and gnanulocyte differentiation uti- lizing highly specific monoclonal antibodies that define cell surface antigens in conjunction with more traditional markers such as surface and cytoplasmic immunoglobulin on B lymphocytes, sheep

Kenneth A. Foon; Robert W. Schroff; Robert Peter Gale; Wendell F. Rosse; Joseph Yourno; Peter Burkart; Walter Mastropaolo; Anthony Tartaglia; James D. Griffin; Richard P. Beveridge; Stuart F. Schlossman; Mark R. Wick; Chin-Yang Li; Robert V. Pierre; Carl G. Figdor; Willy S. Bont; Ivo Touw; Johan de Roos; Eddy E. Roosnek; Jan E. de Vries; Thomas J. Kunicki; Mary B. Koenig; Susan M. Kristopeit; Richard H. Aster; Paula B. Tracy; Lisa L. Eide; E. J. W. Bowie; Kenneth G. Mann

1982-01-01

245

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.

246

Chronic B-Cell Leukemias and Agent Orange  

MedlinePLUS

... Orange » Chronic B-cell Leukemias and Agent Orange Public Health Public Health Public Health Home Military Exposures Military Exposures Home 4 Ways ... Publications & Reports About Us About the Office of Public Health Post-Deployment Health Clinical Public Health About Clinical ...

247

Autologous and allogeneic stem cell transplantation for chronic lymphocytic leukemia  

Microsoft Academic Search

Allogeneic and autologous stem cell transplantation (SCT) are increasingly considered for treatment of patients with chronic lymphocytic leukemia (CLL). In order to assess the potential therapeutic value of SCT for CLL, the present article aims at answering the following crucial questions: (1) Is SCT a curative treatment? (2) Does SCT improve the prognosis of poor-risk CLL? (3) Do risk factors

P Dreger; E Montserrat

2002-01-01

248

[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

249

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

250

Significantly Better Prognosis for Patients with Primary Plasma Cell Leukemia than for Patients with Secondary Plasma Cell Leukemia  

Microsoft Academic Search

Plasma cell leukemia (PCL) is a rare variant of multiple myeloma (MM). Patients may either present de novo (primary PCL), or PCL may occur during the course of MM (secondary PCL). We compared the laboratory and clinical findings of both primary and secondary PCL and MM to elucidate their natural history and the relationship among these entities. Ten cases of

Choong Hwan Cha; Chan Jeoung Park; Joo Ryung Huh; Hyun Sook Chi; Cheol Won Suh; Yoon Koo Kang

2007-01-01

251

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.

252

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

253

Hairy leukoplakia--a histological study.  

PubMed

Hairy leukoplakia is a recently described oral mucosal condition seen in immunosuppressed individuals, usually in association with HIV infection, when it is thought to be a sign of decreasing immunocompetence. It probably results from reactivation of infection by Epstein-Barr virus (EBV) and usually presents as bilateral white patches on the lateral borders of the tongue. From a histological study of 20 cases we have found that the typical appearance of hairy leukoplakia is of acanthotic, hyperparakeratinized epithelium with Candida hyphae sometimes present in the parakeratin. A band of EBV infected, koilocyte-like cells is present in the upper part of the prickle cell layers, these cells being swollen and pale staining, with prominent cell borders and perinuclear vacuoles. There is a paucity of inflammation in both the epithelium and lamina propria. An atypical appearance shows the koilocyte-like cells lying isolated or in small groups, irregularly arranged in the prickle cell layer and without a hyperparakeratinized surface. Diagnosis of hairy leukoplakia should normally be confirmed by demonstrating EBV in the koilocyte-like cells by immunocytochemistry or DNA in situ hybridization. PMID:1655610

Southam, J C; Felix, D H; Wray, D; Cubie, H A

1991-07-01

254

Expression of CD1d by myelomonocytic leukemias provides a target for cytotoxic NKT cells  

Microsoft Academic Search

Natural killer T (NKT) cells with an invariant T-cell receptor for ?-galactosylceramide (?GalCer) that is presented by CD1d have been reported to be cytotoxic for myelomonocytic leukemia cells. However, the necessity for leukemia cell CD1d expression, the role of ?GalCer, and the cytotoxic mechanisms have not been fully elucidated. We evaluated these issues with myeloid leukemia cells from 14 patients

L S Metelitsa; K I Weinberg; P D Emanuel; R C Seeger

2003-01-01

255

The molecular basis of T cell acute lymphoblastic leukemia  

PubMed Central

T cell acute lymphoblastic leukemias (T-ALLs) arise from the malignant transformation of hematopoietic progenitors primed toward T cell development, as result of a multistep oncogenic process involving constitutive activation of NOTCH signaling and genetic alterations in transcription factors, signaling oncogenes, and tumor suppressors. Notably, these genetic alterations define distinct molecular groups of T-ALL with specific gene expression signatures and clinicobiological features. This review summarizes recent advances in our understanding of the molecular genetics of T-ALL.

Van Vlierberghe, Pieter; Ferrando, Adolfo

2012-01-01

256

Inhibition of histone methyltransferase EZH2 depletes leukemia stem cell of mixed lineage leukemia fusion leukemia through upregulation of p16.  

PubMed

Leukemia stem cells (LSC) are resistant to conventional chemotherapy and persistent LSC after chemotherapy are supposed to be a major cause of relapse. However, information on genetic or epigenetic regulation of stem cell properties is still limited and LSC-targeted drugs have scarcely been identified. Epigenetic regulators are associated with many cellular processes including maintenance of stem cells. Of note are polycomb group proteins, because they potentially control stemness, and can be pharmacologically targeted by a selective inhibitor (DZNep). Therefore, we investigated the therapeutic potential of EZH2 inhibition in mixed lineage leukemia (MLL) fusion leukemia. Intriguingly, EZH2 inhibition by DZNep or shRNA not only suppressed MLL fusion leukemia proliferation but also reduced leukemia initiating cells (LIC) frequency. Expression analysis suggested that p16 upregulation was responsible for LICs reduction. Knockdown of p16 canceled the survival advantage of mice treated with DZNep. Chromatin immunoprecipitation assays demonstrated that EZH2 was highly enriched around the transcription-start-site of p16, together with H3K27 methylation marks in MLL/ENL and Hoxa9/Meis1 transduced cells but not in E2A/HLF transduced cells. Although high expression of Hoxa9 in MLL fusion leukemia is supposed to be responsible for the recruitment of EZH2, our data also suggest that there may be some other mechanisms independent of Hoxa9 activation to suppress p16 expression, because expression levels of Hoxa9 and p16 were not inversely related between MLL/ENL and Hoxa9/Meis1 transduced cells. In summary, our findings show that EZH2 is a potential therapeutic target of MLL fusion leukemia stem cells. PMID:24612037

Ueda, Koki; Yoshimi, Akihide; Kagoya, Yuki; Nishikawa, Satoshi; Marquez, Victor E; Nakagawa, Masahiro; Kurokawa, Mineo

2014-05-01

257

Leukemia and Hematopoietic Stem Cells: Balancing Proliferation and Quiescence  

PubMed Central

Chromosomal translocations that disrupt transcriptional regulators are frequently involved in the etiology of leukemia. To gain an understanding of the normal and pathologic roles of these transcriptional regulators, both gain- and loss-of-function mutations have been examined in the context of steady-state hematopoiesis. These studies have identified a remarkable number of genes whose loss-of-function phenotype includes a perturbation of hematopoietic stem cell (HSC) proliferation. As more of these models are generated and analyzed using commonly available tools, the regulatory pathways that control HSC quiescence and proliferation are becoming clearer. An emerging theme is that leukemia-associated transcriptional regulators coordinate the balance of proliferation and quiescence within the HSC pool by modulating the number and frequency of cells transiting the cell cycle. Uncoupling proliferation from differentiation by the aberrant generation of chimeric oncogenes that retain some, but not all of the attributes of the original transcription factor is likely to be an important step during leukemogenesis.

Jude, Craig D.; Gaudet, Justin; Speck, Nancy; Ernst, Patricia

2010-01-01

258

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.

259

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

ClinicalTrials.gov

B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Diffuse Large Cell Lymphoma; L3 Childhood Acute Lymphoblastic Leukemia; Stage III Childhood Large Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma; Untreated Childhood Acute Lymphoblastic Leukemia

2014-02-05

260

Retinoic acids induce growth inhibition and apoptosis in adult T-cell leukemia (ATL) cell lines  

Microsoft Academic Search

Adult T-cell leukemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukemia virus type I (HTLV-I). Despite the administration of combined intensive chemotherapy, the reported survival time of patients with acute and lymphoma types of ATL is less than 10 months. We therefore examine the effects of all-trans-retinoic acid (ATRA), 9-cis-RA and 13-cis-RA and tried to elucidate the

Satoshi Fujimura; Junji Suzumiya; Keizo Anzai; Kumiko Ohkubo; Tomoko Hata; Yasuaki Yamada; Shimeru Kamihira; Masahiro Kikuchi; Junko Ono

1998-01-01

261

Acute myeloid leukemia  

MedlinePLUS

... For information on other types of leukemia, see: Chronic lymphocytic leukemia (CLL) Chronic myelogenous leukemia (CML) Leukemia ... number of platelets. A white blood cell count ( WBC ) is usually high but can be low or ...

262

Generation of leukemia-specific T-helper type 1 cells applicable to human leukemia cell-therapy  

Microsoft Academic Search

Leukemic dendritic cells (DC) were induced from the peripheral blood (PB) or bone marrow (BM) of leukemia patients by culture with (i) GM-CSF + IL-3 (neutral condition); (ii) GM-CSF + IL-3 + IL-12 + IFN-? (type 1-condition); or (iii) GM-CSF + IL-3 + IL-4 (type 2-condition). Although leukemic cells rapidly differentiated into adhesive leukemic DC in all culture conditions, type1-conditions

Taku Fujimura; Kenji Chamoto; Takemasa Tsuji; Takeshi Sato; Hiroshi Yokouchi; Setsuya Aiba; Hachiro Tagami; Junji Tanaka; Masahiro Imamura; Yuji Togashi; Toshiaki Koda; Takashi Nishimura

2004-01-01

263

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.

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

2010-01-01

264

T-cell phenotypes in chemically induced leukemia in mice.  

PubMed

T-cell leukemias were induced in adult BDF mice by a single i.v. injection of 50 mg kg-1 of methylnitrosourea (MNU). Leukemic cells from the thymus and other organ sites showed the theta antigen and were peanut-negative, but were heterogeneous with respect to Lyt-1 and Lyt-2. The acute cytotoxic effect of the MNU showed no preferential toxicity to a special T-cell subset in the thymus. During the latency period of leukemogenesis a continuous fall in peanut-positive cells in the thymus was found. PMID:3872975

Kreja, L; Hartmann, W; Seidel, H J

1985-01-01

265

Three new monoclonal antibodies that define a unique antigen associated with prolymphocytic leukemia/non-Hodgkin's lymphoma and are effectively internalized after binding to the cell surface antigen.  

PubMed

Prolymphocytic leukemia (PLL) is closely related to chronic lymphocytic leukemia (CLL), but present with distinctive clinical/laboratory features and associated with much worse prognosis. In this study, we generated three new IgG1-kappa monoclonal antibodies (MoAbs), termed SN8, SN8a and SN8b, by use of an unconventional approach, ie, by using an isolated B PLL antigen preparation to immunize mice. These MoAbs, particularly SN8, showed a highly selective reactivity to B PLL and B non-Hodgkin's lymphoma (NHL) among various human leukemia-lymphoma specimens tested; eg, SN8 was capable of effectively distinguishing B PLL from B CLL as well as from hairy cell leukemia (HCL) cell specimens. The cell surface antigen defined by the three MoAbs was determined to be a covalently linked heterodimeric glycoprotein complex (gp49/40) consisting of a 49,000 dalton (alpha-chain) and a 40,000-dalton component (beta-chain). Epitope comparison showed that the epitope defined by SN8 (SN8 epitope) is in close proximity to SN8a epitope but in a distant position from SN8b epitope. Western blot analysis showed that both SN8 and SN8a epitopes are on the beta-chain, but SN8b epitope was not detected on either the alpha- or the beta-chain of the reduced antigen in the same analysis. Binding of either SN8 or SN8b to the cell surface gp49/40 did not cause significant downregulation of the antigen expression whereas binding of SN8a to the antigen caused small (approximately 20%) decrease in the antigen expression. Among the various normal peripheral blood cells, only a subpopulation (6.0% to 24.2% among different specimens derived from different donors) of B cells reacted with the SN8 series MoAbs; these MoAbs showed no significant reactivity against T cells, granulocytes, monocytes, erythrocytes, and platelets. Minimal or no significant reactivity (0 to 2.6% among different specimens) was detected against normal bone marrow cells. Ricin A-chain conjugates of the three MoAbs are all strongly effective for specific killing of SN8 antigen-expressing leukemia cells in the absence of any potentiators; furthermore, the addition of 10 mmol/L NH4Cl, a potentiator, enhanced strongly the cytotoxic activities of the SN8, SN8a, and SN8b conjugates. Thus, each of the three MoAbs was effectively internalized after binding to the cell surface antigen. PMID:8417805

Okazaki, M; Luo, Y; Han, T; Yoshida, M; Seon, B K

1993-01-01

266

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.

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

267

Reprogramming of MLL-AF9 leukemia cells into pluripotent stem cells.  

PubMed

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

2014-05-01

268

Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukemia  

PubMed Central

Tissue stromal cells interact with leukemia cells and profoundly affect their viability and drug sensitivity. Here we show a biochemical mechanism by which bone marrow stromal cells modulate the redox status of chronic lymphocytic leukemia (CLL) cells and promote cellular survival and drug resistance. Primary CLL cells from patients exhibit limited ability to transport cystine for glutathione (GSH) synthesis due to a low expression of Xc- transporter, while bone marrow stromal cells effectively import cystine and convert it to cysteine, which is then released into the microenvironment for uptake by CLL cells to promote GSH synthesis. The elevated GSH enhances leukemia cell survival and protects them from drug-induced cytotoxicity. Furthermore, disabling this protective mechanism significantly sensitizes CLL cells to drug treatment in stromal environment. This stromal-leukemia interaction is critical for CLL cell survival and represents a key biochemical pathway for effectively targeting leukemia cells to overcome drug resistance in vivo.

Zhang, Wan; Trachootham, Dunyaporn; Liu, Jinyun; Chen, Gang; Pelicano, Helene; Garcia-Prieto, Celia; Lu, Weiqin; Burger, Jan A; Croce, Carlo M; Plunkett, William; Keating, Michael J; Huang, Peng

2012-01-01

269

ATM Mutations in B-Cell Chronic Lymphocytic Leukemia  

Microsoft Academic Search

Mutations in the ATM gene located on the long arm of chromosome 11 at 11q22-23 cause ataxia-telangiectasia, an autosomal recessive disorder that is associated with increased incidence of malignancy and, particu- larly, lymphoid tumors. A role for ATM in the development of sporadic T-cell chronic leukemias is supported by the finding of loss of heterozy- gosity at 11q22-23 and ATM

Florencia Bullrich; Debora Rasio; Shinichi Kitada; Petr Starostik; Thomas Kipps; Michael Keating; Maher Albitar; John C. Reed; Carlo M. Croce

270

M ultimarker Analysis of T-Cell Chronic Lymphocytic Leukemia  

Microsoft Academic Search

A 68-yr-old male with chronic lymphocytic leukemia (CLL) presented with spleno- megaly and skin infiltration but no lymphadenopathy. The peripheral blood WBC count was 300 x 109\\/liter, with 95% small mature-appearing lympho- cytes that were E-rosette positive and EAC-rosette negative. Further characteri- zation of the patient's cells was performed using antisera with known lymphoid sub- population specificity. Anti-p23,30, which reacts

Saul Yanovich; David S. Rosenthal; William C. Moloney; Stuart F. Schlossman

1978-01-01

271

Oncogenic Kras Initiates Leukemia in Hematopoietic Stem Cells  

Microsoft Academic Search

How oncogenes modulate the self-renewal properties of cancer-initiating cells is incompletely understood. Activating KRAS and NRAS mutations are among the most common oncogenic lesions detected in human cancer, and occur in myeloproliferative disorders (MPDs) and leukemias. We investigated the effects of expressing oncogenic KrasG12D from its endogenous locus on the proliferation and tumor-initiating properties of murine hematopoietic stem and progenitor

Amit J Sabnis; Laurene S Cheung; Monique Dail; Hio Chung Kang; Marianne Santaguida; Michelle L Hermiston; Emmanuelle Passegué; Kevin Shannon; Benjamin S Braun

2009-01-01

272

Plasma cell leukemia with lobulated nuclei: One case report  

Microsoft Academic Search

The case of an 80-year-old man with plasma cell leukemia characterized by basophilic cytoplasm, and extensive lobulated nuclei\\u000a is described. In spite of the peculiar morphologic nuclei, the diagnosis was based on the presence of M protein and Bence\\u000a Jones protein in the serum and urine, immunophenotypic characteristics, immunoglobulin gene rearrangement, and findings of\\u000a transmission electron microscopy.

Kunio Yano; Masahide Kobayashi; Kazunari Iijima; Kazunori Kawane; Sumiko Hamanaka

1997-01-01

273

Genetic aberrations and survival in plasma cell leukemia  

Microsoft Academic Search

Plasma cell leukemia (PCL) is an aggressive and rare hematological malignancy that originates either as primary disease (pPCL) or as a secondary leukemic transformation (sPCL) of multiple myeloma (MM). We report here the genetic aberrations and survival of 80 patients with pPCL or sPCL and make comparisons with 439 cases of MM. pPCL presents a decade earlier than sPCL (54.7

R E Tiedemann; N Gonzalez-Paz; R A Kyle; R Santana-Davila; T Price-Troska; S A Van Wier; W J Chng; R P Ketterling; M A Gertz; K Henderson; P R Greipp; A Dispenzieri; M Q Lacy; S V Rajkumar; P L Bergsagel; A K Stewart; R Fonseca

2008-01-01

274

Increased bone marrow angiogenesis in B cell chronic lymphocytic leukemia  

Microsoft Academic Search

Recent studies have shown that angiogenesis may be involved in the pathogenesis of hematopoietic malignancies, apart from its well-characterized role in the growth and metastasis of solid tumors. In this study, we quantified the degree of angiogenesis in B cell chronic lymphocytic leukemia (B-CLL) by measuring the microvessel density and hotspot density in bone marrow trephine biopsy sections with B-CLL

AR Kini; NE Kay; LC Peterson; LAC Peterson

2000-01-01

275

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

2014-07-15

276

High frequencies of leukemia stem cells in poor-outcome childhood precursor-B acute lymphoblastic leukemias  

PubMed Central

In order to develop a xenograft model to determine the efficacy of new therapies against primary human precursor-B acute lymphoblastic leukemia (ALL) stem cells (LSCs), we used the highly immunodeficient non-obese diabetic (NOD).Cg-PrkdcscidIL2rgtmlWjl/SzJ (NOD-severe combined immune deficient (scid) IL2rg?/?) mouse strain. Intravenous transplantation of 2 of 2 ALL cell lines and 9 of 14 primary ALL cases generated leukemia-like proliferations in recipient mice by 1–7 months after transplant. Leukemias were retransplantable, and the immunophenotypes, gene rearrangements and expression profiles were identical or similar to those of the original primary samples. NOD-scid mice transplanted with the same primary samples developed similar leukemias with only a slightly longer latency than did NOD-scid-IL2Rg?/? mice. In this highly sensitive NOD-scid-IL2Rg?/?-based assay, 1–100 unsorted primary human ALL cells from five of five tested patients, four of whom eventually experienced leukemia relapse, generated leukemias in recipient mice. This very high frequency of LSCs suggests that a hierarchical LSC model is not valuable for poor-outcome ALL.

Morisot, S; Wayne, A S; Bohana-Kashtan, O; Kaplan, I M; Gocke, C D; Hildreth, R; Stetler-Stevenson, M; Walker, R L; Davis, S; Meltzer, P S; Wheelan, S J; Brown, P; Jones, R J; Shultz, L D; Civin, C I

2010-01-01

277

Combination Chemotherapy with Bortezomib, Cyclophosphamide and Dexamethasone may be Effective for Plasma Cell Leukemia  

Microsoft Academic Search

Plasma cell leukemia is a rare malignant plasma cell disorder characterized by proliferation of plasma cells in blood and the bone marrow, the outcome of which is poor with conventional therapy. More effective treatment strategies are therefore needed for this disorder. Here, we report a case of secondary plasma cell leukemia from Immunoglobulin D multiple myeloma refractory to doxorubicin-containing chemotherapy

Seok Jin Kim; Jeeyong Kim; Yunjung Cho; Bo Kyoung Seo; Byung Soo Kim

278

B-cell leukemia/lymphoma panel  

MedlinePLUS

B lymphocyte cell surface markers ... is any bleeding. 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. ...

279

TLX1 and NOTCH coregulate transcription in T cell acute lymphoblastic leukemia cells  

Microsoft Academic Search

BACKGROUND: The homeobox gene TLX1 (for T-cell leukemia homeobox 1, previously known as HOX11) is inappropriately expressed in a major subgroup of T cell acute lymphoblastic leukemia (T-ALL) where it is strongly associated with activating NOTCH1 mutations. Despite the recognition that these genetic lesions cooperate in leukemogenesis, there have been no mechanistic studies addressing how TLX1 and NOTCH1 functionally interact

Irene Riz; Teresa S Hawley; Truong V Luu; Norman H Lee; Robert G Hawley

2010-01-01

280

FGF2 abnormalities in B cell chronic lymphocytic and chronic myeloid leukemias  

Microsoft Academic Search

An elevated level of fibroblast growth factor-2 (FGF-2) in peripheral blood is considered to play a role in regulating the growth of leukemia cells. Here, we show that the level of plasma FGF-2 is increased in 54% of B cell chronic lymphocytic leukemias (B-CLL) and in 44% of chronic myeloid leukemias (CML). Notably, white blood cells (WBCs) from B-CLL patients

P Krej?í; D Dvo?áková; E Krahulcová; J Pacherník; J Mayer; A Hampl; P Dvo?ák

2001-01-01

281

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

PubMed Central

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

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

2014-01-01

282

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

PubMed

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

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

2014-05-01

283

Testican 3 expression in adult T-cell leukemia.  

PubMed

Adult T-cell leukemia (ATL) is an aggressive disease characterized by visceral invasion, and ATL regulates matrix metalloproteinase (MMP) activities of the endothelial cells. The controlling system of MMP activities in ATL is regulated by various factors such as Emmprin and tissue inhibitor of MMP. In this study, we demonstrated that Testican 3 expression in ATL decreased the activity of MMP. Furthermore, we showed that the expression of Testican 3 was regulated by activating transcriptional factor 3 in human T-lymphotropic virus type I-related cell lines. Thus, Testican 3 is a novel regulator to reduce the activity of MMP in ATL. PMID:19144404

Kamioka, Mikio; Imamura, Jun; Komatsu, Naoki; Daibata, Masanori; Sugiura, Tetsuro

2009-07-01

284

Bone Marrow Stromal Cells Modulate Mouse ENT1 Activity and Protect Leukemia Cells from Cytarabine Induced Apoptosis  

PubMed Central

Background Despite a high response rate to chemotherapy, the majority of patients with acute myeloid leukemia (AML) are destined to relapse due to residual disease in the bone marrow (BM). The tumor microenvironment is increasingly being recognized as a critical factor in mediating cancer cell survival and drug resistance. In this study, we propose to identify mechanisms involved in the chemoprotection conferred by the BM stroma to leukemia cells. Methods Using a leukemia mouse model and a human leukemia cell line, we studied the interaction of leukemia cells with the BM microenvironment. We evaluated in vivo and in vitro leukemia cell chemoprotection to different cytotoxic agents mediated by the BM stroma. Leukemia cell apoptosis was assessed by flow cytometry and western blotting. The activity of the equilibrative nucleoside transporter 1 (ENT1), responsible for cytarabine cell incorporation, was investigated by measuring transport and intracellular accumulation of 3H-adenosine. Results Leukemia cell mobilization from the bone marrow into peripheral blood in vivo using a CXCR4 inhibitor induced chemo-sensitization of leukemia cells to cytarabine, which translated into a prolonged survival advantage in our mouse leukemia model. In vitro, the BM stromal cells secreted a soluble factor that mediated significant chemoprotection to leukemia cells from cytarabine induced apoptosis. Furthermore, the BM stromal cell supernatant induced a 50% reduction of the ENT1 activity in leukemia cells, reducing the incorporation of cytarabine. No protection was observed when radiation or other cytotoxic agents such as etoposide, cisplatin and 5-fluorouracil were used. Conclusion The BM stroma secretes a soluble factor that significantly protects leukemia cells from cytarabine-induced apoptosis and blocks ENT1 activity. Strategies that modify the chemo-protective effects mediated by the BM microenvironment may enhance the benefit of conventional chemotherapy for patients with AML.

Macanas-Pirard, Patricia; Leisewitz, Andrea; Broekhuizen, Richard; Cautivo, Kelly; Barriga, Francisco M.; Leisewitz, Francisco; Gidi, Victoria; Riquelme, Erick; Montecinos, Viviana P.; Swett, Pilar; Besa, Pelayo; Ramirez, Pablo; Ocqueteau, Mauricio; Kalergis, Alexis M.; Holt, Matthew; Rettig, Michael; DiPersio, John F.; Nervi, Bruno

2012-01-01

285

Preferential eradication of acute myelogenous leukemia stem cells by fenretinide  

PubMed Central

Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression, and relapse, and thus represent a critical target for therapeutic intervention. However, relatively few agents have been shown to target LSCs, slowing progress in the treatment of acute myelogenous leukemia (AML). Based on in vitro and in vivo evidence, we report here that fenretinide, a well-tolerated vitamin A derivative, is capable of eradicating LSCs but not normal hematopoietic progenitor/stem cells at physiologically achievable concentrations. Fenretinide exerted a selective cytotoxic effect on primary AML CD34+ cells, especially the LSC-enriched CD34+CD38? subpopulation, whereas no significant effect was observed on normal counterparts. Methylcellulose colony formation assays further showed that fenretinide significantly suppressed the formation of colonies derived from AML CD34+ cells but not those from normal CD34+ cells. Moreover, fenretinide significantly reduced the in vivo engraftment of AML stem cells but not normal hematopoietic stem cells in a nonobese diabetic/SCID mouse xenotransplantation model. Mechanistic studies revealed that fenretinide-induced cell death was linked to a series of characteristic events, including the rapid generation of reactive oxygen species, induction of genes associated with stress responses and apoptosis, and repression of genes involved in NF-?B and Wnt signaling. Further bioinformatic analysis revealed that the fenretinide–down-regulated genes were significantly correlated with the existing poor-prognosis signatures in AML patients. Based on these findings, we propose that fenretinide is a potent agent that selectively targets LSCs, and may be of value in the treatment of AML.

Zhang, Hui; Mi, Jian-Qing; Fang, Hai; Wang, Zhao; Wang, Chun; Wu, Lin; Zhang, Bin; Minden, Mark; Yang, Wen-Tao; Wang, Huan-Wei; Li, Jun-Min; Xi, Xiao-Dong; Chen, Sai-Juan; Zhang, Ji; Chen, Zhu; Wang, Kan-Kan

2013-01-01

286

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

ClinicalTrials.gov

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

2013-10-30

287

PHF6 mutations in T-cell acute lymphoblastic leukemia  

PubMed Central

Tumor suppressor genes on the X chromosome may skew the gender distribution of specific types of cancer1,2. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with an increased incidence in males3. In this study, we report the identification of inactivating mutations and deletions in the X-linked plant homeodomain finger 6 (PHF6) gene in 16% of pediatric and 38% of adult primary T-ALL samples. Notably, PHF6 mutations are almost exclusively found in T-ALL samples from male subjects. Mutational loss of PHF6 is significantly associated with leukemias driven by aberrant expression of the homeobox transcription factor oncogenes TLX1 and TLX3. Overall, these results identify PHF6 as a new X-linked tumor suppressor in T-ALL and point to a strong genetic interaction between PHF6 loss and aberrant expression of TLX transcription factors in the pathogenesis of this disease.

Van Vlierberghe, Pieter; Palomero, Teresa; Khiabanian, Hossein; Van der Meulen, Joni; Castillo, Mireia; Van Roy, Nadine; De Moerloose, Barbara; Philippe, Jan; Gonzalez-Garcia, Sara; Toribio, Maria L; Taghon, Tom; Zuurbier, Linda; Cauwelier, Barbara; Harrison, Christine J; Schwab, Claire; Pisecker, Markus; Strehl, Sabine; Langerak, Anton W; Gecz, Jozef; Sonneveld, Edwin; Pieters, Rob; Paietta, Elisabeth; Rowe, Jacob M; Wiernik, Peter H; Benoit, Yves; Soulier, Jean; Poppe, Bruce; Yao, Xiaopan; Cordon-Cardo, Carlos; Meijerink, Jules; Rabadan, Raul; Speleman, Frank; Ferrando, Adolfo

2010-01-01

288

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

2014-07-09

289

Dendritic cell-based immunogens for B-cell chronic lymphocytic leukemia  

Microsoft Academic Search

Hybrids generated from tumor cells and dendritic cells (DC) have been proposed as tools for treating malignant disease. Here, we study the underlying principles and the feasibility for the adjuvant therapy of human B cell chronic-lymphocytic leukemia (B-CLL). CLL cells and allogeneic DC were only mixed or additionally fused. Using a combination of FACS and fluorescence microscopic analyses, we show

Thomas Allgeier; Silke Garhammer; Elfriede Nößner; Ulrich Wahl; Konrad Kronenberger; Martin Dreyling; Michael Hallek; Ralph Mocikat

2007-01-01

290

Ultrastructural Characteristics of the Plasma Cells of a Patient with Nonsecretory Myeloma and Plasma Cell Leukemia  

Microsoft Academic Search

The clinical features and the ultrastructural findings of the bone marrow and peripheral blood plasma cells of a patient with nonsecretory myeloma and acute plasma cell leukemia are described. The internal ultrastructure of the cells was characterized by invaginated nuclei, cytoplasmic filaments and scanty endoplasmic reticulum. Scanning electron microscopy examination revealed the presence of numerous membranal buddings giving the cells

H. Bassan; H. Gutmann; M.. Djaldetti

1981-01-01

291

Hematopoietic stem cells and progenitors of chronic myeloid leukemia express leukemia-associated antigens: implications for the graft-versus-leukemia effect and peptide vaccine-based immunotherapy  

PubMed Central

The cure of chronic myeloid leukemia (CML) patients following allogeneic stem cell transplantation (SCT) is attributed to graft-versus-leukemia (GVL) effects targeting alloantigens and/or leukemia-associated antigens (LAA) on leukemia cells. To assess the potential of LAA-peptide vaccines in eliminating leukemia in CML patients, we measured WT1, PR3, ELA2 and PRAME expression in CD34+ progenitor subpopulations in CML patients and compared them with minor histocompatibility antigens (mHAgs) HA1 and SMCY. All CD34+ subpopulations expressed similar levels of mHAgs irrespective of disease phase, suggesting that in the SCT setting, mHAgs are the best target for GVL. Furthermore, WT1 was consistently overexpressed in advanced phase (AdP) CML in all CD34+ subpopulations, and mature progenitors of chronic phase (CP) CML compared to healthy individuals. PRAME overexpression was limited to more mature AdP-CML progenitors only. Conversely, only CP-CML progenitors had PR3 overexpression, suggesting that PR1-peptide vaccines are only appropriate in CP-CML. Surface expression of WT1 protein in the most primitive hematopoietic stem cells in AdP-CML suggest that they could be targets for WT1 peptide-based vaccines, which in combination with PRAME, could additionally improve targeting differentiated progeny, and benefit patients responding suboptimally to tyrosine kinase inhibitors, or enhance GVL effects in SCT patients.

Yong, Agnes S. M.; Keyvanfar, Keyvan; Eniafe, Rhoda; Savani, Bipin N.; Rezvani, Katayoun; Sloand, Elaine M.; Goldman, John M.; Barrett, A. John

2008-01-01

292

Feasible production of camptothecin by hairy root culture of Ophiorrhiza pumila  

Microsoft Academic Search

Camptothecin derivatives are used clinically as anti-tumor alkaloids. Camptothecin and its related compounds are at present obtained by extraction from intact plants, but transformed plant cell cultures may be an alternative source of production. We have established a hairy root culture of Ophiorriza pumila (Rubiaceae) transformed by Agrobacterium rhizogenes strain 15834. This hairy root culture grew well, increasing by 16-fold

K. Saito; H. Sudo; M. Yamazaki; M. Koseki-Nakamura; M. Kitajima; H. Takayama; N. Aimi

2001-01-01

293

Overexpression of glucosylceramide synthase in associated with multidrug resistance of leukemia cells  

Microsoft Academic Search

Ceramide, as a second messenger, initiates one of the major signal transduction pathways in tumor apoptosis. Glucosylceramide synthase (GCS) catalyzes glycosylation of ceramide and produces glucosylceramide. Through GCS, ceramide glycosylation allows cellular escape from ceramide-induced programmed cell death. Here we investigated the expression of GCS in human leukemia cells and an association between GCS and multidrug resistance of leukemia cells.

Ping Xie; Yun-Fen Shen; Yuan-Ping Shi; Shu-Mei Ge; Zhong-Hua Gu; Jue Wang; Hui-Jun Mu; Bin Zhang; Wei-Zhen Qiao; Ke-Ming Xie

2008-01-01

294

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

Microsoft Academic Search

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

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

2001-01-01

295

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

Microsoft Academic Search

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

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

296

T-cell Prolymphocytic Leukemia Presenting as Red Eye  

PubMed Central

T-cell prolymphocytic leukemia (T-PLL) is a rare, highly aggressive, mature T-cell neoplasm. Ocular involvement in T-PLL is very rarely described in the literature. There are only two reports in the literature documenting conjunctival involvement in cases with T-PLL. Conjunctival involvement may be the presenting sign of the disease or rarely signifies the relapse of the disease. We present a case of a 36-year-old Saudi male patient in whom bilateral red eyes were the presenting sign of T-PLL.

Alwadani, Fahad

2011-01-01

297

Blinatumomab induces autologous T-cell killing of chronic lymphocytic leukemia cells  

PubMed Central

Chronic lymphocytic leukemia is an incurable B-cell malignancy that is associated with tumor cell-mediated T-cell dysfunction. It therefore represents a challenging disease for T-cell immunotherapeutics. The CD19/CD3 bi-specific antibody construct blinatumomab (AMG103 or MT103) has been tested clinically in non-Hodgkin’s lymphoma and acute lymphoblastic leukemia but has not been assessed in chronic lymphocytic leukemia. We investigated whether blinatumomab could overcome T-cell dysfunction in chronic lymphocytic leukemia in vitro. Blinatumomab was tested on peripheral blood mononuclear cells from 28 patients (treatment naïve and previously treated). T-cell activation and function, as well as cytotoxicity against leukemic tumor cells were measured. Blinatumomab induced T-cell activation, proliferation, cytokine secretion and granzyme B release in a manner similar to that occurring with stimulation with anti-CD3/anti-CD28 beads. However, only blinatumomab was able to induce tumor cell death and this was found to require blinatumomab-mediated conjugate formation between T cells and tumor cells. Cytotoxicity of tumor cells was observed at very low T-cell:tumor cell ratios. A three-dimensional model based on confocal microscopy suggested that up to 11 tumor cells could cluster round each T cell. Importantly, blinatumomab induced cytotoxicity against tumor cells in samples from both treatment-naïve and treated patients, and in the presence of co-culture pro-survival signals. The potent cytotoxic action of blinatumomab on tumor cells appears to involve conjugation of T cells with tumor cells at both the activation and effector stages. The efficacy of blinatumomab in vitro suggests that the bi-specific antibody approach may be a powerful immunotherapeutic strategy in chronic lymphocytic leukemia.

Wong, Ryan; Pepper, Chris; Brennan, Paul; Nagorsen, Dirk; Man, Stephen; Fegan, Chris

2013-01-01

298

Two species of type C viral core polyprotein on AKR mouse leukemia cells.  

PubMed Central

Two species of glycosylated type C viral core polyprotein were identified on the surface of AKR spontaneous leukemia cells. One of these cell surface polyproteins was shown by immunoprecipitation to have antigenic determinants of murine leukemia virus p30, p15, p12, and p10; the other had murine leukemia virus p30, p15, and p12, but not p10, determinants. Both species were also expressed on thymocytes from 6-month-old, preleukemic AKR mice. Images

Tung, J S; Pinter, A; Fleissner, E

1977-01-01

299

Retinoic acid signaling regulates embryonic clock hairy2 gene expression in the developing chick limb.  

PubMed

Embryo development proceeds under strict temporal control and an embryonic molecular clock (EC), evidenced by cyclic gene expression, is operating during somite formation and limb development, providing temporal information to precursor cells. In somite precursor cells, EC gene expression and periodicity depends on Retinoic acid (RA) signaling and this morphogen is also essential for limb initiation, outgrowth and patterning. Since the limb EC gene hairy2 is differentially expressed along the proximal-distal axis as growth proceeds, concomitant with changes in flank-derived RA activity in the mesenchyme, we have interrogated the role of RA signaling on limb hairy2 expression regulation. We describe RA as a positive regulator of limb hairy2 expression. Ectopic supplementation of RA induced hairy2 in a short time period, with simultaneous transient activation of Erk/MAPK, Akt/PI3K and Gli3 intracellular pathways. We further found that FGF8, an inducer of Erk/MAPK, Akt/PI3K pathways, was not sufficient for ectopic hairy2 induction. However, joint treatment with both RA and FGF8 induced hairy2, indicating that RA is creating a permissive condition for p-Erk/p-Akt action on hairy2, most likely by enhancing Gli3-A/Gli3-R levels. Finally, we observed an inhibitory action of BMP4 on hairy2 and propose a model whereby RA shapes limb hairy2 expression during limb development, by activating its expression and counteracting the inhibitory action of BMP4 on hairy2. Overall, our work reports a novel role for RA in the regulation of limb clock hairy2 gene expression and elucidates the temporal response of multiple intracellular pathways to RA signaling in limb development. PMID:22728880

Sheeba, Caroline J; Palmeirim, Isabel; Andrade, Raquel P

2012-07-13

300

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

Microsoft Academic Search

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

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

2011-01-01

301

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

Microsoft Academic Search

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

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

2012-01-01

302

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

303

T-cell acute lymphoblastic leukemia after liver transplant.  

PubMed

T-cell posttransplant lymphoproliferative disorders after solid-organ transplant are rare and may be clinically aggressive. A 3-year-old boy had liver transplant from his grandfather because of hepatoblastoma. The immunosuppressive regimen was based on tacrolimus and prednisolone. At 22 months after transplant (age, 5 years), the patient presented to the hospital because of severe cough. Computed tomography scan of the chest showed a large left mediastinal mass (9 × 7.2 × 7 cm) and left pleural effusion. A Tru-Cut biopsy of the mediastinal mass showed diffuse infiltration with blast cells, and the diagnosis of T-cell acute lymphoblastic leukemia was made. Immunohistochemical examination of blasts showed strong and diffuse terminal deoxynucleotidyl transferase and CD3 antibody expression; Ki-67 proliferation index was > 95%, and tumor cells were negative for Epstein-Barr virus. Tacrolimus was stopped, sirolimus was started, and chemotherapy was given, but he died 2 months after diagnosis because of chemotherapy-induced sepsis. Monomorphic T-cell posttransplant lymphoproliferative disorder with features of acute lymphoblastic leukemia and lymphoblastic lymphoma is rare after liver transplant. PMID:24635812

Akar Özkan, Eylem; Özdemir, B Handan; Y?lmaz Akçay, Eda; Ok At?lgan, Alev; Haberal, Mehmet

2014-03-01

304

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

305

Leukemia  

MedlinePLUS

... That Affect Blood Cells Click for more information Myeloma and lymphoma are other types of cancer that ... cells are rarely found in the blood stream. Myeloma is the second most common form of blood ...

306

Boosting leukemia-specific T cell responses in patients following stem cell transplantation  

PubMed Central

Whole tumor cell-based vaccines administered within the first 2 to 3 months after allogeneic stem cell transplantation stand out as a promising approach to enhance graft-vs.-leukemia responses. Herein, the implications of this finding for the development of strategies to improve the outcome of patients subjected to allogeneic stem cell transplantation are discussed.

Burkhardt, Ute E; Wu, Catherine J

2013-01-01

307

Haploidentical stem cell transplantation used in treating primary plasma cell leukemia: a case report  

Microsoft Academic Search

Here we report a successful protocol in treatment of a patient with primary plasma cell leukemia (PPCL) using haploidentical stem cell transplantation (hi-HSCT). During first complete remission after routine chemotherapy, the patient received autologous blood stem cell transplantation, but he had relapse later. He gained a second CR after chemotherapy and underwent hi-HSCT from his daughter, who had HLA mismatched

Ouyang Guifang; Zhu Huiling; Hong Yongwei; Xu Kaihong; Mu Qitian; Le Jing; Wu Wenmiao; Lu Ying; Gu Xuewei; Ni Lifeng

2010-01-01

308

Plasma cell leukemia 3 months after autologous blood cell transplantation for multiple myeloma  

Microsoft Academic Search

We describe a patient with multiple myeloma who was treated with intensive therapy and autologous blood cell transplantation as her first-line treatment. The disease relapsed 3 months after the transplant as plasma cell leukemia and the patient succumbed in 4 weeks. We suggest that an aggressive plasma cell clone may be selected during the course of intensive treatment. Complex karyotypic

K Koskela; T-T Pelliniemi; T Lakkala; K Remes

1998-01-01

309

Selected epidemiologic observations of cell-specific leukemia mortality in the United States, 1969-1977  

SciTech Connect

Utilizing a newly available data set which includes for the first time cell-specific leukemia mortality rates for the United States during 1969-1977, age and sex distributions, time trends and geographic patterns were analyzed. Four major cell types of leukemia were considered. Acute lymphatic leukemia had a bimodal distribution with the first peak in the 5-9-year age group and lowest rates in age group 35-44, after which rates rose geometrically. Acute myeloid leukemia had only a very small childhood peak with a low in the age group 5-9, after which the rates also rose geometrically. For both chronic lymphatic and myeloid leukemia the rates rose geometrically after age 15. Rates among females were consistently lower for each age group. The highest sex ratio was found for chronic lymphatic leukemia and is proposed to be the result of a lag period between male and female rates. During the period under study acute lymphatic leukemia mortality in adults declined by almost 10% while acute myeloid leukemia mortality increased by almost 20%. Analysis of the geographic variation of the four major cell types revealed a geographic association between acute lymphatic and acute myeloid leukemia in children, a lack of association between childhood and adult cell types, and an association of acute and chronic cell types in adults.

Selvin, S.; Levin, L.I.; Merrill, D.W.; Winkelstein, W. Jr.

1983-01-01

310

Selected epidemiological observations of cell-specific leukemia mortality in the USA, 1969-1977  

SciTech Connect

Utilizing a newly available data set which includes for the first time cell-specific leukemia mortality rates for the USA during the period 1969-1977, age and sex distributions, time trends and geographic patterns have been analyzed. Four major cell types of leukemia were considered. Acute lymphatic leukemia had a bimodal distribution with the first peak in the 5 to 9 year age group and lowest rates in age group 35 to 44 after which rates rose geometrically. Acute myeloid leukemia had only a very small childhood peak with a low in the age group 5 to 9, after which the rates also rose geometrically. For both chronic lymphatic and myeloid leukemia the rates rose geometrically after age 15. Rates among females were consistently lower for each age group. The highest sex ratio was found for chronic lymhatic leukemia and is proposed to be the result of a lag period between male and female rates. During the period under study acute lymphatic leukemia mortality in adults declined by almost 10% while acute myeloid leukemia mortality increased by almost 20%. Analysis of the geographic variation of the four major cell types revealed a geographic association between acute lymphatic and acute myeloid leukemia in children, a lack of association between childhood and adult cell types and an association of acute and chronic cell types in adults.

Selvin, S.; Levin, L.I.; Merrill, D.W.; Winkelstein, W. Jr.

1982-03-01

311

Method for differential diagnosis of T cell leukemias using monoclonal antibodies  

SciTech Connect

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

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

1987-02-24

312

CREB antisense oligonucleotides induce non-apoptotic cell death in proliferating leukemia cells, but not normal hematopoietic cells, by a bizarre non-antisense mechanism  

Microsoft Academic Search

We report that antisense phosphorothioate oligodeoxyribonucleotides (PS-ODNs) against cyclic AMP response element-binding protein (CREB) induce the death of human leukemia cell lines including HL-60, Kasumi-1 and K562, OCI-AML1a and also primary leukemia cells isolated from patients with acute myelocytic leukemia and chronic myelocytic leukemia in blastic crisis. In contrast, normal human bone marrow CD34+ cells and normal peripheral blood lymphocytes

K Saeki; A Yuo; M Koizumi; K Fujiwara; M Kaneko; F Takaku; Y Yazaki

2001-01-01

313

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

2014-04-16

314

Oncogenic Kras Initiates Leukemia in Hematopoietic Stem Cells  

PubMed Central

How oncogenes modulate the self-renewal properties of cancer-initiating cells is incompletely understood. Activating KRAS and NRAS mutations are among the most common oncogenic lesions detected in human cancer, and occur in myeloproliferative disorders (MPDs) and leukemias. We investigated the effects of expressing oncogenic KrasG12D from its endogenous locus on the proliferation and tumor-initiating properties of murine hematopoietic stem and progenitor cells. MPD could be initiated by KrasG12D expression in a highly restricted population enriched for hematopoietic stem cells (HSCs), but not in common myeloid progenitors. KrasG12D HSCs demonstrated a marked in vivo competitive advantage over wild-type cells. KrasG12D expression also increased the fraction of proliferating HSCs and reduced the overall size of this compartment. Transplanted KrasG12D HSCs efficiently initiated acute T-lineage leukemia/lymphoma, which was associated with secondary Notch1 mutations in thymocytes. We conclude that MPD-initiating activity is restricted to the HSC compartment in KrasG12D mice, and that distinct self-renewing populations with cooperating mutations emerge during cancer progression.

Sabnis, Amit J; Cheung, Laurene S; Dail, Monique; Kang, Hio Chung; Santaguida, Marianne; Hermiston, Michelle L; Passegue, Emmanuelle; Shannon, Kevin; Braun, Benjamin S

2009-01-01

315

Blocking p55PIK signaling inhibits proliferation and induces differentiation of leukemia cells  

PubMed Central

p55PIK, a regulatory subunit of phosphatidylinositol 3-kinases, promotes cell cycle progression by interacting with cell cycle modulators such as retinoblastoma protein (Rb) via its unique amino-terminal 24 amino-acid residue (N24). Overexpression of N24 specifically inhibits these interactions and leads to cell cycle arrest. Herein, we describe the generation of a fusion protein (Tat transactivator protein (TAT)–N24) that contains the protein transduction domain and N24, and examined its effects on the proliferation and differentiation of leukemia cells. TAT–N24 not only blocks cell proliferation but remarkably induces differentiation of leukemia cells in vitro and in vivo. Systemically administered TAT–N24 also significantly decreases growth of leukemia cell tumors in animal models. Furthermore, overexpression of p55PIK in leukemia cells leads to increased proliferation; however, TAT–N24 blocks this effect and concomitantly induces differentiation. There is significant upregulation of p55PIK mRNA and protein expression in leukemia cells from patients. TAT–N24 inhibits cell cycle progression and induces differentiation of bone marrow cells derived from patients with several different types of leukemia. These results show that cell-permeable N24 peptide induces leukemia cell differentiation and suggest that p55PIK may be a novel drug target for the treatment of hematopoetic malignancies.

Wang, G; Deng, Y; Cao, X; Lai, S; Tong, Y; Luo, X; Feng, Y; Xia, X; Gong, J; Hu, J

2012-01-01

316

Long-term cultivation of plasma cell leukemia cells and autologous lymphoblasts (LCL) in vitro: A comparative study  

Microsoft Academic Search

Summary Two long-term cell lines were established in vitro from the peripheral blood of a patient with plasma cell leukemia: one line with plasma cell proliferation, the other with lymphoblastoid cell proliferation (LCL).

V. Diehl; M. Schaadt; H. Kirchner; K.-P. Hellriegel; F. Gudat; C. Fonatsch; E. Laskewitz; R. Guggenheim

1978-01-01

317

SSBP2, a candidate tumor suppressor gene, induces growth arrest and differentiation of myeloid leukemia cells  

Microsoft Academic Search

Acute myelogenous leukemia (AML) is the most common leukemia in adults with clonal proliferation of myeloid stem cells. Two or more cooperating mechanisms, namely block in differentiation, enhanced proliferation and resistance to programmed cell death, underlie this neoplastic transformation. Nonrandom, complete and partial deletions of chromosome 5 are common anomalies in AML. Using positional cloning strategies, we characterized an evolutionarily

Hong Liang; Susmita Samanta; Lalitha Nagarajan

2005-01-01

318

Identification of therapeutic targets for quiescent, chemotherapy-resistant human leukemia stem cells  

Microsoft Academic Search

Human acute myeloid leukemia (AML) originates from rare leukemia stem cells (LSCs). Because these chemotherapy-resistant LSCs are thought to underlie disease relapse, effective therapeutic strategies specifically targeting these cells may be beneficial. Here, we report identification of a primary human LSC gene signature and functional characterization of human LSC-specific molecules in vivo in a mouse xenotransplantation model. In 32 of

Y. Saito; H. Kitamura; A. Hijikata; Murasawa M Tomizawa; S. Tanaka; H Ozawa; A Wake; S Taniguchi; L D Shultz; O Ohara; F. Ishikawa

2010-01-01

319

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.

320

[Plasmacytoïd dendritic cells acute leukemia: a case report].  

PubMed

We describe a case of a patient hospitalized in haematology unit for treatment to blastic plasmacytoid dendritic cell neoplasm. Apart skin lesions found at diagnosis in 83% of patients, few elements suggest the diagnosis. Cytology is not characteristic and no cytogenetic abnormality is specific to the LpDC, the karyotype shows generally at least three cytogenetic abnormalities. Definitive diagnosis rests to identification of a blastic population with immunophenotype CD4+ CD56+. This leukemia is chemosensitive but the relapse rate is important and the survival time is 16 months. PMID:23047909

Bousquet, Aurore; Doutrelon, Caroline; Konopacki, Johanna; Marfaing-Koka, Anne; Segot, Amandine; Martinaud, Christophe; Samson, Thierry; Souleau, Bertrand; Malfuson, Jean-Valère; De Revel, Thierry; Foissaud, Vincent

2012-10-01

321

Molecular profiling reveals myeloid leukemia cell lines to be faithful model systems characterized by distinct genomic aberrations  

Microsoft Academic Search

To model and investigate different facets of leukemia pathogenesis, a widely accepted approach is to use immortalized leukemia cell lines. Although these provide powerful tools to our knowledge, few studies have addressed the question whether hematopoietic cell lines represent accurate and reliable model systems. To improve the molecular characterization of these model systems, we analyzed 17 myeloid leukemia cell lines

F G Rücker; S Sander; K Döhner; H Döhner; J R Pollack; L Bullinger

2006-01-01

322

Improving the Outcome of Leukemia by Natural Killer Cell-Based Immunotherapeutic Strategies  

PubMed Central

Blurring the boundary between innate and adaptive immune system, natural killer (NK) cells are widely recognized as potent anti-leukemia mediators. Alloreactive donor NK cells have been shown to improve the outcome of allogeneic stem-cell transplantation for leukemia. In addition, in vivo transfer of NK cells may soon reveal an important therapeutic tool for leukemia, if tolerance to NK-mediated anti-leukemia effects is overcome. This will require, at a minimum, the ex vivo generation of a clinically safe NK cell product containing adequate numbers of NK cells with robust anti-leukemia potential. Ideally, ex vivo generated NK cells should also have similar anti-leukemia potential in different patients, and be easy to obtain for convenient clinical scale-up. Moreover, optimal clinical protocols for NK therapy in leukemia and other cancers are still lacking. These and other issues are being currently addressed by multiple research groups. This review will first describe current laboratory NK cell expansion and differentiation techniques by separately addressing different NK cell sources. Subsequently, it will address the mechanisms known to be responsible for NK cell alloreactivity, as well as their clinical impact in the hematopoietic stem cells transplantation setting. Finally, it will briefly provide insight on past NK-based clinical trials.

Chouaib, Salem; Pittari, Gianfranco; Nanbakhsh, Arash; El Ayoubi, Hanadi; Amsellem, Sophie; Bourhis, Jean-Henri; Spanholtz, Jan

2014-01-01

323

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

324

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

2014-04-07

325

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

326

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

PubMed

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

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

2014-03-17

327

Prodigiosin induces apoptosis of B and T cells from B-cell chronic lymphocytic leukemia  

Microsoft Academic Search

We have previously reported that prodigiosin (2-methyl-3-pentyl-6-methoxyprodigiosene) induces apoptosis in human hematopoietic cancer cell lines with no marked toxicity in nonmalignant cell lines. In this study, we demonstrate that prodigiosin induces apoptosis of B-cell chronic lymphocytic leukemia (B-CLL) cells (n=32 patients). The dose–response for the cytotoxic effect of prodigiosin was analyzed in cells from 12 patients showing an IC50 of

C Campàs; M Dalmau; B Montaner; M Barragán; B Bellosillo; D Colomer; G Pons; R Pérez-Tomás; J Gil

2003-01-01

328

Biological activity of DC-CIK cells and its effect against leukemia cells in vitro.  

PubMed

This study was aimed to investigate the effect of dendritic cells (DC) on the proliferation capability, immunophenotype changes, level of secreted cytokines and activity against leukemia of cytokine-induced killer (CIK) cells in vitro. DCs and CIK cells were induced from peripheral blood mononuclear cells of healthy volunteers. They were co-cultured meanwhile CIK cells were cultured alone as controls. Increased number of cells were counted by trypan-blue staining; the killing activity was detected by MTT assay; immunophenotype changes were analyzed by flow cytometry; the IL-12 and INF-gamma levels of the cultured supernatants were detected by ELISA kits. The results showed that the proliferation capability of DC-CIK cells was significantly higher than that of CIK cells (p < 0.05). Under the same condition, the ratio of double positive cells such as CD3(+) CD8(+), CD3(+) CD56(+) in CIK cells was significantly enhanced by co-cultured with DC cells (p < 0.05). The levels of IL-12 and INF-gamma in cultured supernatants of DC-CIK cells increased noticeably on day 3 as compared with CIK cells cultured alone (p < 0.01, p < 0.05). Within the effector-target ratio range between 5:1 to 40:1, the activity of DC-CIK cells against leukemia cells were much higher than that of CIK cells (p < 0.05), and this effect showed a positive correlation with the effector-target ratio. It is concluded that the proliferation capability of DC-CIK cells, the level of their secreted cytokines and their activity against leukemia cells are significantly higher than those of CIK cells. This research may suggest an approach for clinical immunotherapy against leukemia with DC-CIK cells. PMID:18928615

Wei, Xu-Cang; Zhai, Xin-Hui; Han, Xiu-Rui; Yang, Di-Di; Zhao, Wen-Li

2008-10-01

329

Method and Agent for Inducing Apoptosis/Cell Death in Leukemia Cells  

National Technical Information Service (NTIS)

A method for inducing apoptosis or cell death in leukemia cells includesinhibiting the production of nitric oxide (NO) by using a nitric oxide synthase (NOS) inhibitor, or the actions of NO by a NO quencher/scavenger. The NOS inhibitor includes a NOS1-spe...

J. B. Weinberg M. C. Levesque D. K. Ghosh

2004-01-01

330

Generation of multi-leukemia antigen-specific T cells to enhance the graft-versus-leukemia effect after allogeneic stem cell transplant.  

PubMed

Adoptive immunotherapy with ex vivo expanded T cells is a promising approach to prevent or treat leukemia. Myeloid leukemias express tumor-associated antigens (TAA) that induce antigen-specific cytotoxic T lymphocyte (CTL) responses in healthy individuals. We explored the feasibility of generating TAA-specific CTLs from stem cell donors of patients with myeloid leukemia to enhance the graft-versus-leukemia effect after stem cell transplantation. CTL lines were manufactured from peripheral blood of 10 healthy donors by stimulation with 15mer peptide libraries of five TAA (proteinase 3 (Pr3), preferentially expressed antigen in melanoma, Wilms tumor gene 1 (WT1), human neutrophil elastase (NE) and melanoma-associated antigen A3) known to be expressed in myeloid leukemias. All CTL lines responded to the mix of five TAA and were multi-specific as assessed by interferon-? enzyme-linked immunospot. Although donors showed individual patterns of antigen recognition, all responded comparably to the TAAmix. Immunogenic peptides of WT1, Pr3 or NE could be identified by epitope mapping in all donor CTL lines. In vitro experiments showed recognition of partially human leukocyte antigen (HLA)-matched myeloid leukemia blasts. These findings support the development of a single clinical grade multi-tumor antigen-specific T-cell product from the stem cell source, capable of broad reactivity against myeloid malignancies for use in donor-recipient pairs without limitation to a certain HLA-type. PMID:23528871

Weber, G; Gerdemann, U; Caruana, I; Savoldo, B; Hensel, N F; Rabin, K R; Shpall, E J; Melenhorst, J J; Leen, A M; Barrett, A J; Bollard, C M

2013-07-01

331

Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an Interleukin 8-dependent survival of leukemia cells.  

PubMed

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by the Bcr-Abl oncoprotein with constitutive tyrosine kinase activity. Exosomes are nanovesicles released by cancer cells that are involved in cell-to-cell communication thus potentially affecting cancer progression. It is well known that bone marrow stromal microenvironment contributes to disease progression through the establishment of a bi-directional crosstalk with cancer cells. Our hypothesis is that exosomes could have a functional role in this crosstalk. Interleukin-8 (IL 8) is a proinflammatory chemokine that activates multiple signalling pathways downstream of two receptors (CXCR1 and CXCR2). We demonstrated that exosomes released from CML cells stimulate bone marrow stromal cells to produce IL 8 that, in turn, is able to modulate both in vitro and in vivo the leukemia cell malignant phenotype. PMID:24657661

Corrado, Chiara; Raimondo, Stefania; Saieva, Laura; Flugy, Anna Maria; De Leo, Giacomo; Alessandro, Riccardo

2014-06-28

332

Cochlear implantation in a patient with acute myelomonocytic leukemia before allogeneic peripheral blood stem cell transplantation.  

PubMed

Bilateral deafness can occur in patients with acute leukemia and it can cause communication problems and depressed mood during the treatment of leukemia. Cochlear implantation (CI) is the choice of hearing rehabilitation; however, there is scarce information about the safety of CI during the treatment of leukemia. A 50-year-old female leukemia patient was successfully implanted with a Nucleus cochlear implant while in complete remission before peripheral blood stem cell transplantation. Until now, with a follow-up of 4 years, the patient has useful hearing perception without any complications. To our knowledge, this is the first reported case of a successful CI in a patient with acute leukemia during the treatment of leukemia. PMID:24560096

Cho, Hyong-Ho; Lee, Sungsu; Cho, Yong-Beom

2014-08-01

333

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

PubMed Central

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

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

2011-01-01

334

Dipyridamole enhancement of drug sensitivity in acute lymphoblastic leukemia cells.  

PubMed

The effect of dipyridamole (DPM) on cell sensitivity to anticancer drugs was examined in acute lymphoblastic leukemia (ALL) cell lines. We established two ALL cell lines (KMO-90 and KMO-R) from bone marrow samples of a 12-year-old girl with ALL. The drug concentrations needed to reduce optical density to 50% of that of control cells (IC50) showed that KMO-R was about twofold more resistant to doxorubicin (DOX), mitoxantrone (MIT), vincristine (VCR), and etoposide (VP-16) than was KMO-90. Considering that both KMO-90 and KMO-R were established from a patient with ALL at the time of presentation and relapse, respectively, these two cell lines might be novel and useful models for research into the acquisition of drug resistance in ALL cells. Although cytotoxicity of DPM in KMO-90 was about 6% at 1 microgram/ml, DPM enhanced cell sensitivity to DOX, MIT, VCR, and VP-16 at this concentration. Cytotoxicity of DPM in KMO-R was less than 5% at 1, 5, and 10 micrograms/ml. In KMO-R, DPM enhanced cell sensitivity to these four drugs in a dose-dependent manner. The plasma concentrations achieved by oral administration of DPM is about 1 microgram/ml. At clinically achievable concentrations, DPM enhanced cell sensitivity to DOX, MIT, VCR, and VP-16 in both KMO-90 and KMO-R, thus showing DPM to be a useful agent for potentiating anticancer chemotherapy of hematopoietic malignancy. PMID:8372807

Sotomatsu, M; Yugami, S; Shitara, T; Kuroume, T

1993-08-01

335

Effects of Manisa propolis on telomerase activity in leukemia cells obtained from the bone marrow of leukemia patients.  

PubMed

Propolis is a resinous material collected by honeybees and obtained from beehives that has anticancer effects by inducing apoptosis. The aim of this study is to investigate the effect of propolis on human telomerase reverse transcriptase (hTERT) in the leukemia cells obtained from leukemia patients. Four different bone marrow cell cultures from each of four leukemia cases were prepared. The 60 ng/ml, 30 ng/ml and 15 ng/ml working concentrations of propolis were administered to three cultures of each patient, while one culture contained only culture medium. hTERT mRNA expression levels of cells were detected at 24 h, 48 h and 72 h using the LightCycler 2.0 instrument. A significant decrease in hTERT expression levels was observed in the 60 ng/ml concentration of propolis. In conclusion, Manisa propolis may also have a potential effect on the expression of hTERT in leukemia-particularly owing to its constituent chrysin. PMID:19817639

Cogulu, O; Biray, C; Gunduz, C; Karaca, E; Aksoylar, S; Sorkun, K; Salih, B; Ozkinay, F

2009-11-01

336

Natural Antibodies to Human Retrovirus HTLV in a Cluster of Japanese Patients with Adult T Cell Leukemia  

Microsoft Academic Search

Human T cell lymphoma leukemia virus (HTLV) is a human retrovirus (RNA tumor virus) that was originally isolated from a few patients with leukemias or lymphomas involving mature T lymphocytes. Here we report that the serum of Japanese patients with adult T cell leukemia, but not the serum of tested normal donors, contains high titers of antibodies to HTLV. These

Marjorie Robert-Guroff; Yoshinobu Nakao; Kunihiro Notake; Yohei Ito; Ann Sliski; Robert C. Gallo

1982-01-01

337

Prognostic relevance of RUNX1 mutations in T-cell acute lymphoblastic leukemia  

PubMed Central

The runt-related transcription factor 1, RUNX1, is crucial in the development of myeloid and lymphoid cell lineages and has been reported to be mutated in myeloid malignancies in approximately 30% of cases. In this study, the mutational status of RUNX1 was investigated in 128 acute lymphoblastic leukemia patients. We detected a mutation rate of 18.3% (13 of 71) in patients with T-cell acute lymphoblastic leukemia, 3.8% (2 of 52) in patients with B-cell acute lymphoblastic leukemia and no mutation (0 of 5) in patients with natural killer cell leukemia, respectively. In T-cell acute lymphoblastic leukemia patients, RUNX1 mutations were significantly associated with higher age (P=0.017) and lower white blood cell count (P=0.038). Moreover, an inferior outcome was observed in the subgroup of early T-cell acute lymphoblastic leukemia patients carrying RUNX1 mutations for overall survival (P=0.043). In conclusion, RUNX1 mutations are an important novel biomarker for a comprehensive characterization of T-cell acute lymphoblastic leukemia with poor prognostic impact and have implications for use also in monitoring disease.

Grossmann, Vera; Kern, Wolfgang; Harbich, Stefan; Alpermann, Tamara; Jeromin, Sabine; Schnittger, Susanne; Haferlach, Claudia; Haferlach, Torsten; Kohlmann, Alexander

2011-01-01

338

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

339

Bone morphogenetic proteins regulate differentiation of human promyelocytic leukemia cells.  

PubMed

We investigated the role of bone morphogenetic proteins (BMPs) in suppression of all-trans retinoic acid (ATRA)-mediated differentiation of leukemic promyelocytes. In NB4 and HL60 cell lines, BMPs reduced the percentage of differentiated cells, and suppressed PU.1 and C/EBP? gene expression induced by ATRA. BMP and ATRA synergized in the induction of ID genes, causing suppression of differentiation. In primary acute promyelocytic leukemia bone-marrow samples, positive correlation of PML/RAR? and negative of RAR? with the expression of BMP-4, BMP-6 and ID genes were found. We concluded that BMPs may have oncogenic properties and mediate ATRA resistance by a mechanism that involves ID genes. PMID:23528261

Topi?, Iva; Iki?, Marina; Iv?evi?, Sanja; Kova?i?, Nataša; Maruši?, Ana; Kušec, Rajko; Gr?evi?, Danka

2013-06-01

340

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

341

mTORC1 is essential for leukemia propagation but not stem cell self-renewal  

PubMed Central

Although dysregulation of mTOR complex 1 (mTORC1) promotes leukemogenesis, how mTORC1 affects established leukemia is unclear. We investigated the role of mTORC1 in mouse hematopoiesis using a mouse model of conditional deletion of Raptor, an essential component of mTORC1. Raptor deficiency impaired granulocyte and B cell development but did not alter survival or proliferation of hematopoietic progenitor cells. In a mouse model of acute myeloid leukemia (AML), Raptor deficiency significantly suppressed leukemia progression by causing apoptosis of differentiated, but not undifferentiated, leukemia cells. mTORC1 did not control cell cycle or cell growth in undifferentiated AML cells in vivo. Transplantation of Raptor-deficient undifferentiated AML cells in a limiting dilution revealed that mTORC1 is essential for leukemia initiation. Strikingly, a subset of AML cells with undifferentiated phenotypes survived long-term in the absence of mTORC1 activity. We further demonstrated that the reactivation of mTORC1 in those cells restored their leukemia-initiating capacity. Thus, AML cells lacking mTORC1 activity can self-renew as AML stem cells. Our findings provide mechanistic insight into how residual tumor cells circumvent anticancer therapies and drive tumor recurrence.

Hoshii, Takayuki; Tadokoro, Yuko; Naka, Kazuhito; Ooshio, Takako; Muraguchi, Teruyuki; Sugiyama, Naoyuki; Soga, Tomoyoshi; Araki, Kimi; Yamamura, Ken-ichi; Hirao, Atsushi

2012-01-01

342

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.

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

2014-01-01

343

HI44a, an anti-CD44 monoclonal antibody, induces differentiation and apoptosis of human acute myeloid leukemia cells  

Microsoft Academic Search

CD44 is a cell surface antigen that expresses on leukemia blasts from most acute myeloid leukemia (AML) patients. It has been reported that ligation of CD44 with some specific anti-CD44 monoclonal antibodies can reverse the differentiation blockage of leukemia cell lines. In this study, the differentiation and apoptosis-inducing effects of HI44a, another anti-CD44 monoclonal antibody (IgG2a), were investigated on leukemia

Guoli Song; Xiaolong Liao; Ling Zhou; Lihua Wu; Yi Feng; Zhong Chao Han

2004-01-01

344

Graft-versus-leukemia in a retrovirally induced murine CML model: mechanisms of T-cell killing  

Microsoft Academic Search

The graft-versus-leukemia (GVL) effect, mediated by donor T cells, has revolution- ized the treatment of leukemia. However, effective GVL remains difficult to sepa- rate from graft-versus-host disease (GVHD), and many neoplasms are GVL resistant. Murine studies aimed at solving these problems have been limited by the use of leukemia cell lines with limited homology to human leukemias and by the

Catherine C. Matte; James Cormier; Britt E. Anderson; Ioanna Athanasiadis; Jinli Liu; Stephen G. Emerson; Warren Pear; Warren D. Shlomchik

2004-01-01

345

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.

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

346

RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells.  

PubMed

Ribosomal protein S27a (RPS27a) could perform extra-ribosomal functions besides imparting a role in ribosome biogenesis and post-translational modifications of proteins. The high expression level of RPS27a was reported in solid tumors, and we found that the expression level of RPS27a was up-regulated in advanced-phase chronic myeloid leukemia (CML) and acute leukemia (AL) patients. In this study, we explored the function of RPS27a in leukemia cells by using CML cell line K562 cells and its imatinib resistant cell line K562/G01 cells. It was observed that the expression level of RPS27a was high in K562 cells and even higher in K562/G01 cells. Further analysis revealed that RPS27a knockdown by shRNA in both K562 and K562G01 cells inhibited the cell viability, induced cell cycle arrest at S and G2/M phases and increased cell apoptosis induced by imatinib. Combination of shRNA with imatinib treatment could lead to more cleaved PARP and cleaved caspase-3 expression in RPS27a knockdown cells. Further, it was found that phospho-ERK(p-ERK) and BCL-2 were down-regulated and P21 up-regulated in RPS27a knockdown cells. In conclusion, RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells. It appears that drugs targeting RPS27a combining with tyrosine kinase inhibitor (TKI) might represent a novel therapy strategy in TKI resistant CML patients. PMID:24680683

Wang, Houcai; Yu, Jing; Zhang, Lixia; Xiong, Yuanyuan; Chen, Shuying; Xing, Haiyan; Tian, Zheng; Tang, Kejing; Wei, Hui; Rao, Qing; Wang, Min; Wang, Jianxiang

2014-04-18

347

[Oral hairy leukoplakia in human immunodeficiency virus positive patients: clinical and etiopathogenic aspects].  

PubMed

Clinical and etiopathogenetic features of oral hairy leukoplakia in 5 patients positive for Human Immunodeficiency Virus were studied. Oral hairy leukoplakia were located on the lateral borders of the tongue and showed a corrugated/hairy aspect in all the cases. Histological examination showed hyperparakeratosis, acanthosis, hair like projection (n = 4) koilocyte-like-cells and moderate subepidermal inflammation. Immunohistochemistry revealed positive results for Epstein-Barr virus indicating an active replication of this virus within the epithelial cells of the stratum granulosum and upper stratum spinosum. PMID:1299282

Bujía, J; Riederer, A; Zietz, C; Wilmes, E; Wolf, H

1992-01-01

348

Mechanisms of resistance to azacitidine in human leukemia cell lines.  

PubMed

The DNA methylation inhibitor azacitidine (5-azacytidine) is used against myelodysplastic syndrome and acute myeloid leukemia, but drug resistance is an ongoing, intractable problem. To investigate resistance mechanisms, we generated two azacitidine-resistant cell lines, THP-1/AR and HL60/AR, and studied genetic disparities between them and their corresponding parental lines. In cells treated with azacitidine, significant mitotic variations were noted in parental cells which were absent in resistant cells, suggesting that resistance arises from negating azacitidine-mediated activation of apoptosis signaling and reestablishing G2/M checkpoint. Importantly, both resistant cell lines have common point mutations in the uridine-cytidine kinase 2 (UCK2) gene, which encodes the rate-limiting enzyme of the azacitidine activation pathway. Forced expression of mutated UCK2 in parental THP-1 cells abrogated azacitidine-induced apoptosis, whereas overexpression of wild type UCK2 in resistant THP-1/AR cells restored sensitivity to azacitidine, implying that UCK2 gene mutations perturb azacitidine activation and advance azacitidine resistance. Our study provides new insights into azacitidine resistance and establishes models useful in developing effective strategies to overcome it. PMID:24368162

Sripayap, Piyanuch; Nagai, Tadashi; Uesawa, Mitsuyo; Kobayashi, Hiroyuki; Tsukahara, Tomonori; Ohmine, Ken; Muroi, Kazuo; Ozawa, Keiya

2014-04-01

349

Defective immunoregulatory T-cell function in chronic lymphocytic leukemia  

SciTech Connect

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

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

1981-12-01

350

A novel tetramethylnaphthalene derivative selectively inhibits adult T-cell leukemia (ATL) cells in vitro.  

PubMed

Adult T-cell leukemia (ATL) is caused by infection with human T-cell leukemia virus type-1 (HTLV-1). The tetrahydrotetramethylnaphthalene derivative TMNAA has recently been identified as a selective inhibitor of HTLV-1-infected T-cell lines and adult T-cell leukemia (ATL) cells but not of uninfected T-cell lines and peripheral blood mononuclear cells (PBMCs). In the present study, more than 100 derivatives of TMNAA were synthesized and examined for their inhibitory effects on the proliferation of various T-cell lines and PBMCs. Among the compounds, MN417 is a more potent inhibitor of ATL cells than TMNAA. This compound is a novel phenanthridinone derivative with the tetrahydrotetramethylnaphthalene structure. Interestingly, PN-H and MN314-B, which are also phenanthridinone derivatives but do not have the tetrahydrotetramethylnaphthalene structure, could not distinguish between HTLV-1-infected and uninfected T-cell lines in terms of their anti-proliferative activity. These results suggest that the tetrahydrotetramethylnaphthalene structure is required for the selective inhibition of HTLV-1-infected cells. PMID:24692709

Toyama, Masaaki; Aoyama, Hiroshi; Mukai, Risa; Nakamura, Masaharu; Yoshimura, Koji; Okamoto, Mika; Ohshima, Takayuki; Hashimoto, Yuichi; Baba, Masanori

2014-04-01

351

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

352

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

SciTech Connect

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

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

2010-01-01

353

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

354

Establishment of a Monosomy 7 Leukemia Cell Line, MONO7, With a ras Gene Mutation  

Microsoft Academic Search

A monosomy 7 leukemia cell line, designated MONO-7, was established from the peripheral blood of a patient with monosomy 7\\u000a acute myelocytic leukemia (French-American-British classification M0). The cells were cultured continuously for more than\\u000a 24 months in RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum. The cell line exhibits an unclassified\\u000a appearance. Cytochemically, ?-naphthol-acetate esterase and myeloperoxidase are negative.

Hiroyuki Fujisaki; Kenji Takai; Akihisa Sawada; Sadao Tokimasa; Yoshiko Matsuda; Hideaki Ohta; Yuko Osugi; Ji Yoo Kim; Gaku Hosoi; Masahiro Sako; Junichi Hara

2002-01-01

355

Expression of c-myc is not critical for cell proliferation in established human leukemia lines  

Microsoft Academic Search

BACKGROUND: A study was undertaken to resolve preliminary conflicting results on the proliferation of leukemia cells observed with different c-myc antisense oligonucleotides. RESULTS: RNase H-active, chimeric methylphosphonodiester \\/ phosphodiester antisense oligodeoxynucleotides targeting bases 1147–1166 of c-myc mRNA downregulated c-Myc protein and induced apoptosis and cell cycle arrest respectively in cultures of MOLT-4 and KYO1 human leukemia cells. In contrast, an

David M Tidd; Richard V Giles; Caroline M Broughton; Richard E Clark

2001-01-01

356

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

Microsoft Academic Search

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

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

1998-01-01

357

Glomerulonephritis in chronic lymphocytic leukemia and related B-cell lymphomas  

Microsoft Academic Search

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

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

1992-01-01

358

Role of redox signaling regulation in propyl gallate-induced apoptosis of human leukemia cells  

Microsoft Academic Search

Propyl gallate (PG) is a synthetic antioxidant that has been used in processed food and medicinal preparations. The anti-cancer effect of PG in leukemia is unclear. In the present study, we demonstrate that PG reduced cell viability in THP-1, Jurkat, and HL-60 leukemia cells and induced apoptosis in THP-1 cells. PG activated caspases 3, 8, and 9 and increased the

Ching-Hsein Chen; Wan-Chen Lin; Chien-Neng Kuo; Fung-Jou Lu

2011-01-01

359

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

PubMed Central

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.

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

2013-01-01

360

Apoptosis Induced by the Histone Deacetylase Inhibitor FR901228 in Human T-Cell Leukemia Virus Type 1Infected T-Cell Lines and Primary Adult T-Cell Leukemia Cells  

Microsoft Academic Search

Inhibition of histone deacetylase (HDAC) activity induces growth arrest, differentiation, and, in certain cell types, apoptosis. FR901228, FK228, or depsipeptide, is an HDAC inhibitor effective in T-cell lymphomas. Adult T-cell leukemia (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) and remains incurable. We examined whether FR901228 is effective for treatment of ATL by assessing its ability to

Naoki Mori; Takehiro Matsuda; Masayuki Tadano; Takao Kinjo; Yasuaki Yamada; Kunihiro Tsukasaki; Shuichi Ikeda; Yoshihiro Yamasaki; Yuetsu Tanaka; Takao Ohta; Teruo Iwamasa; Masao Tomonaga; Naoki Yamamoto

2004-01-01

361

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

362

Outcome of allogeneic stem cell transplantation for B cell chronic lymphocytic leukemia  

Microsoft Academic Search

The objective of this study was to describe the outcome of allogeneic stem cell transplantation (alloSCT) in a series of patients with B cell chronic lymphocytic leukemia (B-CLL). Twenty-three B-CLL patients were transplanted between 1988 and 1997 using stem cells from a related (n = 20) or an unrelated donor (n = 3). The median age of the patients was

ZS Pavletic; ER Arrowsmith; PJ Bierman; SA Goodman; JM Vose; SR Tarantolo; RS Stein; G Bociek; JP Greer; CD Wu; JP Kollath; DD Weisenburger; A Kessinger; SN Wolff; JO Armitage

2000-01-01

363

Trisomy 8 in B-cell chronic lymphocytic leukemia.  

PubMed

Association between trisomy 8 and myeloid disorders/malignancies has been well documented. We report on two patients with a known history of B-cell chronic lymphocytic leukemia (B-CLL) with bone marrow involvement. In addition to the classic B-CLL cytogenetic abnormalities in one of the patients, both showed a trisomy 8 clone in their bone marrow specimens. Using a BioView Duet automated scanning system, which allowed us to combine histology with fluorescence in situ hybridization, we showed that the trisomy 8 clone was restricted to the myeloid lineage. We believe that this finding signifies the development of myelodysplastic syndrome (de novo or therapy related), rather than progression of B-CLL with the occurrence of a new clone, and that in general, it has implications for the finding of trisomy 8 in CLL. PMID:18474297

Pozdnyakova, Olga; Stachurski, Dariusz; Hutchinson, Lloyd; Ramakrishnan, Sapna; Miron, Patricia Minehart

2008-05-01

364

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.

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

2014-01-01

365

In Vitro Sensitivity of Leukemia Cells to Propranolol  

PubMed Central

Background Propranolol, as a beta-adrenergic blocker is used for treatment of a large number of cardiovascular diseases such as hypertension and arrhythmias. The inhibitory effects of propranolol on tumor cells growth and also its cytotoxicity on cancerous cells have been revealed by several studies. In this study the sensitivity of a number of human leukemic cell lines to propranolol was evaluated in vitro. Methods Two human leukemic T cells (Molt-4 and Jurkat) and a monocyte (U937) cell line were used in this study. The cells were cultured in complete RPMI medium and then incubated with different concentrations of propranolol (0.0004 -0.4 mM) in the presence or absence of phytoheamagglutinin (20 ?g/ml) for 12, 24 and 48 hours. The cytotoxic effect of the drug was then assessed by trypan blue dye exclusion and also 3-(4,5-dimethyl thiazol-2,5-diphenyltetrazoliumbromide) (MTT) reduction methods. Results Propranolol induced a significant dose dependent cytotoxic effect at ? 0.2 mM concentration on all three human cell lines (Molt-4, Jurkat and U937) used in this study, after 12 hours incubation onwards, compared to untreated control cells. Conclusions Our results demonstrated that leukemic cell lines used in this study were sensitive to propranolol at ? 0.2 mM concentration of the drug. These results suggest that propranolol may have potential implication in chemoprevention of lymphoproliferative disorders along with its chronic long-term usage in cardiac problems. Keywords Propranolol; Leukemia; Cell lines; Sensitivity

Hajighasemi, Fatemeh; Mirshafiey, Abbas

2009-01-01

366

Human Monoclonal Antibody Directed against an Envelope Glycoprotein of Human T-Cell Leukemia Virus Type I  

Microsoft Academic Search

We report the production and characterization of a human monoclonal antibody reactive against the major envelope glycoprotein of human T-cell leukemia virus type I (HTLV-I), a virus linked to the etiology of adult T-cell leukemia. We exposed lymph-node cells derived from a patient with adult T-cell leukemia to the Epstein-Barr virus in vitro and obtained a B-cell clone (designated 0.5alpha

Shuzo Matsushita; Marjorie Robert-Guroff; Jane Trepel; Jeffrey Cossman; Hiroaki Mitsuya; Samuel Broder

1986-01-01

367

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

368

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

369

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

370

Gold nanoparticle-enhanced electroporation for leukemia cell transfection.  

PubMed

Electroporation serves as an attractive nonviral gene delivery approach for its effectiveness, operational simplicity, and no restrictions of probe or cell type. The commercial electroporation systems have been widely adopted in research and clinics with protocols usually compromising appropriate transfection efficiency and cell viability. By introducing gold nanoparticles (AuNPs), we demonstrated greatly enhanced performance of electroporation from two aspects: the highly conductive, naked AuNPs help reduce the potential drop consumed by the electroporation solution so that the majority of the applied voltage of an electric pulse is truly imposed on cells with enhanced field strength; AuNPs with targeting ligands (e.g., transferrin-AuNPs or Tf-AuNPs) are bound to the cell membrane, working as virtual microelectrodes to create pores on cells with limited opening area while from many different sites. The addition of AuNPs during electroporation therefore benefits not only quicker recovery and better survival of cells but also more efficient uptake of the subjected probes. Such enhancement was successfully confirmed on a chronic myeloid leukemia cell line (i.e., K562 cells) in both a commercial batch electroporation system and a homemade flow system with pWizGFP plasmid DNA probes. The efficiency was found to be dependent on the size, concentration, and mixing ratio of free AuNPs/Tf-AuNPs. An equivalent mixture of free AuNPs and Tf-AuNPs exhibited the best enhancement with the transfection efficiency increase of two to threefold at a minimum sacrifice of the cell viability. PMID:24510813

Huang, Shuyan; Zu, Yingbo; Wang, Shengnian

2014-01-01

371

Pro-apoptotic activity of ?-bisabolol in preclinical models of primary human acute leukemia cells  

PubMed Central

Background We previously demonstrated that the plant-derived agent ?-bisabolol enters cells via lipid rafts, binds to the pro-apoptotic Bcl-2 family protein BID, and may induce apoptosis. Here we studied the activity of ?-bisabolol in acute leukemia cells. Methods We tested ex vivo blasts from 42 acute leukemias (14 Philadelphia-negative and 14 Philadelphia-positive B acute lymphoid leukemias, Ph-/Ph+B-ALL; 14 acute myeloid leukemias, AML) for their sensitivity to ?-bisabolol in 24-hour dose-response assays. Concentrations and time were chosen based on CD34+, CD33+my and normal peripheral blood cell sensitivity to increasing ?-bisabolol concentrations for up to 120 hours. Results A clustering analysis of the sensitivity over 24 hours identified three clusters. Cluster 1 (14 ± 5 ?M ?-bisabolol IC50) included mainly Ph-B-ALL cells. AML cells were split into cluster 2 and 3 (45 ± 7 and 65 ± 5 ?M IC50). Ph+B-ALL cells were scattered, but mainly grouped into cluster 2. All leukemias, including 3 imatinib-resistant cases, were eventually responsive, but a subset of B-ALL cells was fairly sensitive to low ?-bisabolol concentrations. ?-bisabolol acted as a pro-apoptotic agent via a direct damage to mitochondrial integrity, which was responsible for the decrease in NADH-supported state 3 respiration and the disruption of the mitochondrial membrane potential. Conclusion Our study provides the first evidence that ?-bisabolol is a pro-apoptotic agent for primary human acute leukemia cells.

2011-01-01

372

Efficient engraftment of primary adult T-cell leukemia cells in newborn NOD\\/SCID\\/?2-microglobulinnull mice  

Microsoft Academic Search

Adult T-cell leukemia (ATL) develops via multiple oncogenic steps in human T-cell leukemia virus type I (HTLV-I) carriers. To better understand pathogenesis of ATL, we developed a novel xenogeneic engraftment model in which primary ATL cells are intravenously transplanted into neonatal nonobese diabetic (NOD)\\/severe-combined immunodeficiency (SCID)\\/?2-microglobulinnull (NOD\\/SCID\\/?2mnull) mice. Acute-type ATL cells engrafted in the peripheral blood and in the lymph

N Kawano; F Ishikawa; K Shimoda; M Yasukawa; K Nagafuji; T Miyamoto; E Baba; T Tanaka; S Yamasaki; H Gondo; T Otsuka; K Ohshima; L D Shultz; K Akashi; M Harada

2005-01-01

373

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

374

Digital gene expression profiling of primary acute lymphoblastic leukemia cells.  

PubMed

We determined the genome-wide digital gene expression (DGE) profiles of primary acute lymphoblastic leukemia (ALL) cells from 21 patients taking advantage of 'second-generation' sequencing technology. Patients included in this study represent four cytogenetically distinct subtypes of B-cell precursor (BCP) ALL and T-cell lineage ALL (T-ALL). The robustness of DGE combined with supervised classification by nearest shrunken centroids (NSC) was validated experimentally and by comparison with published expression data for large sets of ALL samples. Genes that were differentially expressed between BCP ALL subtypes were enriched to distinct signaling pathways with dic(9;20) enriched to TP53 signaling, t(9;22) to interferon signaling, as well as high hyperdiploidy and t(12;21) to apoptosis signaling. We also observed antisense tags expressed from the non-coding strand of ~50% of annotated genes, many of which were expressed in a subtype-specific pattern. Antisense tags from 17 gene regions unambiguously discriminated between the BCP ALL and T-ALL subtypes, and antisense tags from 76 gene regions discriminated between the 4 BCP subtypes. We observed a significant overlap of gene regions with alternative polyadenylation and antisense transcription (P<1 × 10(-15)). Our study using DGE profiling provided new insights into the RNA expression patterns in ALL cells. PMID:22173241

Nordlund, J; Kiialainen, A; Karlberg, O; Berglund, E C; Göransson-Kultima, H; Sønderkær, M; Nielsen, K L; Gustafsson, M G; Behrendtz, M; Forestier, E; Perkkiö, M; Söderhäll, S; Lönnerholm, G; Syvänen, A-C

2012-06-01

375

Digital gene expression profiling of primary acute lymphoblastic leukemia cells  

PubMed Central

We determined the genome-wide digital gene expression (DGE) profiles of primary acute lymphoblastic leukemia (ALL) cells from 21 patients taking advantage of ‘second-generation' sequencing technology. Patients included in this study represent four cytogenetically distinct subtypes of B-cell precursor (BCP) ALL and T-cell lineage ALL (T-ALL). The robustness of DGE combined with supervised classification by nearest shrunken centroids (NSC) was validated experimentally and by comparison with published expression data for large sets of ALL samples. Genes that were differentially expressed between BCP ALL subtypes were enriched to distinct signaling pathways with dic(9;20) enriched to TP53 signaling, t(9;22) to interferon signaling, as well as high hyperdiploidy and t(12;21) to apoptosis signaling. We also observed antisense tags expressed from the non-coding strand of ?50% of annotated genes, many of which were expressed in a subtype-specific pattern. Antisense tags from 17 gene regions unambiguously discriminated between the BCP ALL and T-ALL subtypes, and antisense tags from 76 gene regions discriminated between the 4 BCP subtypes. We observed a significant overlap of gene regions with alternative polyadenylation and antisense transcription (P<1 × 10?15). Our study using DGE profiling provided new insights into the RNA expression patterns in ALL cells.

Nordlund, J; Kiialainen, A; Karlberg, O; Berglund, E C; Goransson-Kultima, H; S?nderkaer, M; Nielsen, K L; Gustafsson, M G; Behrendtz, M; Forestier, E; Perkkio, M; Soderhall, S; Lonnerholm, G; Syvanen, A-C

2012-01-01

376

Spontaneous rupture of the spleen in primary plasma cell leukemia. Scintigraphic-pathologic correlation  

Microsoft Academic Search

A rare case of spontaneous rupture of the spleen occurring in a patient with primary plasma cell leukemia is presented. The scintigraphic-pathologic correlation is presented together with a review of the literature.

G. D. Kienzle; J. Stern; A. Cooperberg; C. A. Osborne

1985-01-01

377

Adult T-cell leukemia: a review of epidemiological evidence.  

PubMed

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

Iwanaga, Masako; Watanabe, Toshiki; Yamaguchi, Kazunari

2012-01-01

378

Enhanced leukemia cell detection using a novel magnetic needle and nanoparticles  

PubMed Central

Acute leukemia is a hematopoietic malignancy for which the accurate measurement of minimal residual disease is critical to determining prognosis and treatment. While bone marrow aspiration and light microscopy remain the current standard of care for detecting residual disease, these approaches cannot reliably discriminate less than 5% lymphoblast cells. To improve the detection of leukemia cells in the marrow, we developed a novel apparatus that employs antibodies conjugated to superparamagnetic iron oxide nanoparticles (SPIONs) and directed against the acute leukemia antigen CD34, coupled with a “magnetic needle” biopsy. Leukemia cell lines expressing high or minimal CD34 were incubated with anti-CD34-conjugated SPIONs. Three separate approaches including microscopy, Superconducting Quantum Interference Device (SQUID) magnetometry, and in vitro magnetic needle extraction were then employed to assess cell sampling. We found that CD34-conjugated nanoparticles preferentially bind high CD34-expressing cell lines. Furthermore, the magnetic needle enabled identification of both cell line and patient leukemia cells diluted into normal blood at concentrations below those normally found in remission marrow samples. Finally, the magnetic needle enhanced the percentage of lymphoblasts detectable by light microscopy by ten-fold in samples of fresh bone marrow aspirate approximating minimal residual disease. These data suggest that bone marrow biopsy using antigen-targeted magnetic nanoparticles and a magnetic needle for the evaluation of minimal residual disease in CD34-positive acute leukemias can significantly enhance sensitivity compared to the current standard of care.

Jaetao, Jason E.; Butler, Kimberly S.; Adolphi, Natalie L.; Lovato, Debbie M.; Bryant, Howard C.; Rabinowitz, Ian; Winter, Stuart S.; Tessier, Trace E.; Hathaway, Helen J.; Bergemann, Christian; Flynn, Edward R.; Larson, Richard S.

2009-01-01

379

Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction  

PubMed Central

The traditional view is that cancer cells predominately produce ATP by glycolysis, rather than by oxidation of energy-providing substrates. Mitochondrial uncoupling — the continuing reduction of oxygen without ATP synthesis — has recently been shown in leukemia cells to circumvent the ability of oxygen to inhibit glycolysis, and may promote the metabolic preference for glycolysis by shifting from pyruvate oxidation to fatty acid oxidation (FAO). Here we have demonstrated that pharmacologic inhibition of FAO with etomoxir or ranolazine inhibited proliferation and sensitized human leukemia cells — cultured alone or on bone marrow stromal cells — to apoptosis induction by ABT-737, a molecule that releases proapoptotic Bcl-2 proteins such as Bak from antiapoptotic family members. Likewise, treatment with the fatty acid synthase/lipolysis inhibitor orlistat also sensitized leukemia cells to ABT-737, which supports the notion that fatty acids promote cell survival. Mechanistically, we generated evidence suggesting that FAO regulates the activity of Bak-dependent mitochondrial permeability transition. Importantly, etomoxir decreased the number of quiescent leukemia progenitor cells in approximately 50% of primary human acute myeloid leukemia samples and, when combined with either ABT-737 or cytosine arabinoside, provided substantial therapeutic benefit in a murine model of leukemia. The results support the concept of FAO inhibitors as a therapeutic strategy in hematological malignancies.

Samudio, Ismael; Harmancey, Romain; Fiegl, Michael; Kantarjian, Hagop; Konopleva, Marina; Korchin, Borys; Kaluarachchi, Kumar; Bornmann, William; Duvvuri, Seshagiri; Taegtmeyer, Heinrich; Andreeff, Michael

2009-01-01

380

Effect of EPH-Ephrin Signaling on the Growth of Human Leukemia Cells.  

PubMed

Background: Signaling induced by binding of erythropoietin-producing hepatoma-amplified sequence (EPH) receptors to their cell-surface ephrin ligands is implicated in hematopoiesis and growth of various cancer cells. However, the roles of EPH-ephrin signaling in leukemia have not been elucidated. We investigated the effects of EPHB4 and ephrin B2 on the growth of leukemia cells. Materials and Methods: Seven human leukemia cell lines were used to examine the effects of recombinant ephrin B2 and EPHB4 on cell proliferation by colorimetric WST-1 assay and colony assays; on protein tyrosine phosphorylation; and on mRNA expression by reverse transcription-polymerase chain reaction and microarray analysis. Results: In an erythroid leukemia-derived cell line AA, exogenous ephrin B2 induced proliferation and colony formation; in addition, it up-regulated protein tyrosine phosphorylation and the expression of growth-related genes such as FBJ murine osteosarcoma viral oncogene homolog B and v-src avian sarcoma viral oncogene homolog. Conclusion: Growth-promoting effects of ephrin B2 were observed in an erythroid leukemia cell line, suggesting that the EPH-ephrin signaling may be involved in the pathology of leukemia. PMID:24922654

Takahashi, Yusuke; Itoh, Mai; Nara, Nobuo; Tohda, Shuji

2014-06-01

381

Chronic lymphocytic leukemia cells are activated and proliferate in response to specific T helper cells.  

PubMed

There is increasing interest in the chronic lymphocytic leukemia (CLL) microenvironment and the mechanisms that may promote CLL cell survival and proliferation. A role for T helper (Th) cells has been suggested, but current evidence is only circumstantial. Here we show that CLL patients had memory Th cells that were specific for endogenous CLL antigens. These Th cells activated autologous CLL cell proliferation in vitro and in human ? mouse xenograft experiments. Moreover, CLL cells were efficient antigen-presenting cells that could endocytose and process complex proteins through antigen uptake pathways, including the B cell receptor. Activation of CLL cells by Th cells was contact and CD40L dependent. The results suggest that CLL is driven by ongoing immune responses related to Th cell-CLL cell interaction. We propose that Th cells support malignant B cells and that they could be targeted in the treatment of CLL. PMID:23933259

Os, Audun; Bürgler, Simone; Ribes, Anna Parente; Funderud, Ane; Wang, Dong; Thompson, Keith M; Tjønnfjord, Geir E; Bogen, Bjarne; Munthe, Ludvig A

2013-08-15

382

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.

383

Biological Properties and Growth in SCID Mice of a New Myelogenous Leukemia Cell Line (KBM-5) Derived from Chronic Myelogenous Leukemia Cells in the Blastic Phase1  

Microsoft Academic Search

The establishment and the biological properties of a new leukemic cell line (KBM-5) derived from a patient in the blastic phase of chronic iny- elogenous leukemia are described. The cells exhibited multiple copies of the Philadelphia chromosome, and a high level of p210Bcr\\

Miloslav Beran; Pavel Pisa; Susan O'Brien; Razelle Kurzrock; Michael Siciliano; Ann Cork; Borje S. Andersson; Vipin Kohli; Hagop Kantarjian

1993-01-01

384

Stem cell transplantation for chronic myeloid leukemia in children.  

PubMed

Hematopoietic stem cell transplantation (SCT) is the only proven cure for chronic myeloid leukemia (CML), a rare disease in childhood. We report outcomes of 314 children with Philadelphia-chromosome-positive (Ph+) CML undergoing SCT from HLA-matched siblings (n = 182) or volunteer-unrelated donors (VUD; n = 132). Three-year overall survival (OS) and leukemia-free survival (LFS) rates were 66% and 55% (n = 314). For 156 children in first chronic phase (CP1) who underwent transplantation from HLA-identical siblings, OS and LFS rates were 75% and 63%. For 97 children who underwent SCT in CP1 from VUD, 3-year OS and LFS rates were 65% and 56%, reflecting higher transplantation-related mortality (TRM) after VUD SCT (35% vs 20%; multivariate hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.0-3.5; P =.05). In a multivariate model for OS and LFS, outcomes were superior in CP1 than in advanced phase (AP/CP1) (OS HR, 2.0; 95% CI, 1.3-3; P =.001; LFS HR, 1.8; 95% CI, 1.2-2.6; P =.003). For relapse, donor source (VUD/sibling) (HR, 0.38; 95% CI, 0.19-0.76; P =.006) and disease stage (AP/CP1) (HR, 2.4; 95% CI, 1.36-4.3; P =.003) were significant. This is the first large series to show that SCT confers long-term LFS in most children with CML and helps assess alternative therapy, including tyrosine kinase inhibitors. PMID:12714525

Cwynarski, Kate; Roberts, Irene A G; Iacobelli, Simona; van Biezen, Anja; Brand, Ronald; Devergie, Agnes; Vossen, Jaak M; Aljurf, Mahmoud; Arcese, William; Locatelli, Franco; Dini, Giorgio; Niethammer, Dietrich; Niederwieser, Dietger; Apperley, Jane F

2003-08-15

385

Isolation and Characterization of Simian T-Cell Leukemia Virus Type II from New World Monkeys  

Microsoft Academic Search

Since the description of human T-cell leukemia virus type I (HTLV-I) and its simian counterpart, simian T-cell leukemia virus type I (STLV-I), the possible existence of other related simian retroviruses has been raised. Here, we report a new retrovirus, STLV-II, which we have identifled in spider monkeys (Áteles fusciceps), a New World primate species. Initially, a recombinant HTLV-II envelope protein

YI-MING A. CHEN; YNG-JU JANG; RICHARD J. MONTALI; PHYLLIS J. KANKI; QIAN-CHUN YU; JAANG-JIUN WANG; KENNETH P. SAMUEL; TAKIS S. PAPAS

386

Primary non-secretory plasma cell leukemia with atypical morphology — a case report  

Microsoft Academic Search

Only one case of primary non-secretory plasma cell leukemia with atypical morphology has been reported thus far. Here we report\\u000a another such case of plasma cell leukemia diagnosed on fl ow cytometry, as morphological heterogeneity and lack of monoclonal\\u000a immunoglobulins in both serum and urine, made it difficult to come to a conclusive diagnosis based purely on morphology.

T. Dadu; A. Rangan; A. Handoo; M. Bhargava

2009-01-01

387

Plasma Cell Leukemia: Case Series From a Tertiary Center with Review of Literature  

Microsoft Academic Search

Plasma cell leukemia is an unusual manifestation of multiple myeloma, reported to occur in 2% of newly diagnosed patients.\\u000a It may either present at the time of diagnosis (primary) or evolve as a late feature in the course of multiple myeloma (secondary).\\u000a Most clinical signs of myeloma are observed in plasma cell leukemia, although osteolytic lesions and bone pain are

Shano Naseem; Sukhpreet Kaur; Ritu Gupta; Rajesh Kashyap; Soniya Nityanand

388

IL18 enhances ULBP2 expression through the MAPK pathway in leukemia cells  

Microsoft Academic Search

Expression of UL16-binding proteins (ULBPs) has been reported in various cancers, such as leukemia and melanoma, and also in some other cancer cell lines. However, the factors that modulate the expression of ULBPs are not well defined. In this study, we investigated the effects of IL-18 on the expression of NKG2D ligands in leukemia cells. IL-18 treatment increased ULBP2 expression

Hyunkeun Song; Kyung-Eun Kim; Daeyoung Hur; Jong-Seok Lim; Young Yang; Byung Joo Cho; Cherl-hyun Kim; Taesung Kim; Saic Bang; Wang Jae Lee; DaeHo Cho

2008-01-01

389

Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms  

Microsoft Academic Search

BACKGROUND: Human T-cell leukemia virus type I (HTLV-I) causes adult T-cell leukemia (ATL) after a long latent period. Among accessory genes encoded by HTLV-I, the tax gene is thought to play a central role in oncogenesis. However, Tax expression is disrupted by several mechanims including genetic changes of the tax gene, deletion\\/hypermethylation of 5'-LTR. To clarify the role of epigenetic

Yuko Taniguchi; Kisato Nosaka; Jun-ichirou Yasunaga; Michiyuki Maeda; Nancy Mueller; Akihiko Okayama; Masao Matsuoka

2005-01-01

390

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

391

Extramedullary Relapse of Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: Different Characteristics between Acute Myelogenous Leukemia and Acute Lymphoblastic Leukemia.  

PubMed

Extramedullary relapse (EMR) of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a contributor to post-transplantation mortality and remains poorly understood, especially the different characteristics of EMR in patients with acute myelogenous leukemia (AML) and those with acute lymphoblastic leukemia (ALL). To investigate the incidence, risk factors, and clinical outcomes of EMR for AML and ALL, we performed a retrospective analysis of 362 patients with AL who underwent allo-HSCT at the First affiliated Hospital of Soochow University between January 2001 and March 2012. Compared with patients with AML, those with ALL had a higher incidence of EMR (12.9% versus 4.6%; P = .009). The most common site of EMR was the central nervous system, especially in the ALL group. Multivariate analyses identified the leading risk factors for EMR in the patients with AML as advanced disease status at HSCT, hyperleukocytosis at diagnosis, history of extramedullary leukemia before HSCT, and a total body irradiation-based conditioning regimen, and the top risk factors for EMR in the patients with ALL as hyperleukocytosis at diagnosis, adverse cytogenetics, and transfusion of peripheral blood stem cells. The prognosis for EMR of AL is poor, and treatment options are very limited; however, the estimated 3-year overall survival (OS) was significantly lower in patients with AML compared with those with ALL (0 versus 18.5%; P = .000). The characteristics of post-allo-HSCT EMR differed between the patients with AML and those with ALL, possibly suggesting different pathogenetic mechanisms for EMR of AML and EMR of ALL after allo-HSCT; further investigation is needed. PMID:24704575

Ge, Ling; Ye, Fan; Mao, Xinliang; Chen, Jia; Sun, Aining; Zhu, Xiaming; Qiu, Huiying; Jin, Zhengming; Miao, Miao; Fu, Chengcheng; Ma, Xiao; Chen, Feng; Xue, Shengli; Ruan, Changgeng; Wu, Depei; Tang, Xiaowen

2014-07-01

392

Identification of the Gross cell surface antigen associated with murine leukemia virus-infected cells.  

PubMed Central

The Gross cell surface antigen (GCSA) is produced by cells that are either exogenously infected with murine leukemia virus (MuLV) or are expressing endogenous MuLV genomes. In immune precipitation assays, GCSA was resolved into two serologically distinct 85,000- and 95,000-dalton viral proteins. These antigenic components are glycosylated forms of the polyprotein precursors of the MuLV internal structural proteins. Images

Ledbetter, J; Nowinski, R C

1977-01-01

393

Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML  

Microsoft Academic Search

Cancer stem cells have been proposed to be important for initiation, maintenance and recurrence of various malignancies, including acute myeloid leukemia (AML). We have previously reported that CD34+CD38- human primary AML stem cells residing in the endosteal region of the bone marrow are relatively chemotherapy resistant. Using a NOD\\/SCID\\/IL2rgamma(null) mouse model of human AML, we now show that the AML

Yoriko Saito; Naoyuki Uchida; Satoshi Tanaka; Nahoko Suzuki; Mariko Tomizawa-Murasawa; Akiko Sone; Yuho Najima; Shinsuke Takagi; Yuki Aoki; Atsushi Wake; Shuichi Taniguchi; Leonard D Shultz; Fumihiko Ishikawa

2010-01-01

394

Cytotoxicity of novel sulfanilamides towards sensitive and multidrugresistant leukemia cells.  

PubMed

Novel sulfa Schiff bases were synthesized and characterized by a reaction between aromatic sulfonamides and aromatic aldehydes or heterocyclic ketones in equimolar ratios. Their cytotoxicity was evaluated by the resazurin assay towards human sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. Three of the tested compounds viz., 4-(anthracen-9-ylmethyleneamino)-N-(pyrimidin-2-yl)benzenesulfonamide (4), 4-(anthracen-9- ylmethyleneamino)benzenesulfonamide, (5) and 4-((3-phenylallylidene)amino)benzene-sulfonamide, (6) were cytotoxic (IC50 values: 5.38-19.96 µM). CEM/ADR5000 cells were not cross-resistant to these compounds, indicating activity against otherwise drug-resistant tumors. Compound 6 inhibited P-glycoprotein by increasing doxorubicin accumulation and reducing expression of P-glycoprotein in CEM/ADR5000 cells. A human P-glycoprotein homology model was used for molecular docking studies. Compound 6 and verapamil (a well-known P-glycoprotein inhibitor) docked with similar binding energies to the same binding pocket. PMID:24438524

AlSalim, T; Saeed, M E M; Hadi, J S; Zeino, M; Gany, R; Kadioglu, O; Titinchi, S J J; Abbo, H S; Efferth, T

2014-01-01

395

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

PubMed

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

Ichim, Christine Victoria

2014-04-01

396

Adult T-cell leukemia cells overexpress Wnt5a and promote osteoclast differentiation  

PubMed Central

Adult T-cell leukemia/lymphoma (ATL) is etiologically linked to infection with the human T-cell leukemia/lymphoma virus type 1 (HTLV-I). ATL is classified into 4 distinct clinical diseases: acute, lymphoma, chronic, and smoldering. Acute ATL is the most aggressive form, representing 60% of cases and has a 4-year survival of <5%. A frequent complication and cause of death in acute ATL patients is the presence of lytic bone lesions and hypercalcemia. We analyzed the Wnt/?-catenin pathway because of its common role in cancer and bone remodeling. Our study demonstrated that ATL cells do not express high levels of ?-catenin but displayed high levels of LEF-1/TCF genes along with elevated levels of ?-catenin (LEF-1/TCF target genes) responsive genes. By profiling Wnt gene expression, we discovered that ATL patient leukemia cells shifted expression toward the noncanonical Wnt pathway. Interestingly, ATL cells overexpressed the osteolytic-associated genes—Wnt5a, PTHLH, and RANKL. We further show that Wnt5a secreted by ATL cells favors osteoclast differentiation and expression of RANK. Our results suggest that Wnt5a is a major contributing factor to the increase in osteolytic bone lesions and hypercalcemia found in ATL patients. Anti-Wnt5a therapy may prevent or reduce osteolytic lesions found in ATL patients and improve therapy outcome.

Bellon, Marcia; Ko, Nga Ling; Lee, Min-Jung; Yao, Yuan; Waldmann, Thomas A.; Trepel, Jane B.

2013-01-01

397

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

PubMed Central

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

2013-01-01

398

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

PubMed

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

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

2014-01-15

399

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

2014-06-30

400

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

2014-04-02

401

Human T-Cell Leukemia Virus Type 1 Tax Oncoprotein Suppression of Multilineage Hematopoiesis of CD34+ Cells In Vitro  

Microsoft Academic Search

Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are highly related viruses that differ in disease manifestation. HTLV-1 is the etiologic agent of adult T-cell leukemia and lymphoma, an aggressive clonal malignancy of human CD4-bearing T lymphocytes. Infection with HTLV-2 has not been conclusively linked to lymphoproliferative disorders. We previously showed that human hematopoietic progenitor (CD34) cells can be

Adam Tripp; Yingxian Liu; Michelle Sieburg; Joanne Montalbano; Stephen Wrzesinski; Gerold Feuer

2003-01-01

402

A newly established human acute lymphoblastic leukemia cell line with characteristics of the earliest B-cell maturation  

Microsoft Academic Search

Summary  A new human acute lymphoblastic leukemia (ALL) cell line, designated HBL-3, was established from the bone marrow of a patient\\u000a with non-T-ALL. The HBL-3 cell line expressed B4 (CD 19), BA-1 (CD 24) and HLA-DR antigens, but not surface immunoglobulin\\u000a (SIg) or cytoplasmic immunoglobulin (CIg). The cell line lacked the common acute lymphoblastic leukemia antigen (CALLA) and\\u000a antigenic markers characteristic

Masafumi Abe; Naoya Nakamura; Shirou Fukuhara; Takamasa Hayashi; Keiki Kawakami; Kenkichi Kita; Toshifumi Kinoshita; Toyoro Ohsato; Haruki Wakasa

1990-01-01

403

Resistance to cyclopentenylcytosine in murine leukemia L1210 cells.  

PubMed

Cyclopentenyl cytosine (CPEC) exhibits oncological activity in murine and human tumor cells and has now entered Phase I clinical trials. Its mode of action as an antitumor agent appears to be inhibition by its triphosphate (CPEC-TP) of CTP synthase, the enzyme which converts UTP to CTP. In an attempt to elucidate the mechanism of resistance to CPEC, a murine leukemia cell line resistant to CPEC (L1210/CPEC) was developed by N-methyl-N-nitro-N-nitrosoguanidine-induced mutagenesis and subsequent selection by cultivation of the L1210 cells in the presence of 2 microM CPEC. Resistant clones were maintained in CPEC-free medium for 6 generations before biochemical studies were performed. The resistant clone selected for further studies was approximately 13,000-fold less sensitive to growth inhibition by CPEC than the parental cells, and the concentration of CPEC required to deplete CTP in the resistant cells was 50-fold higher than in the sensitive cells. A comparison of the kinetic properties of CTP synthase from sensitive and resistant cells indicated alteration in the properties of the enzyme from the latter; the median inhibitory concentration for CPEC-TP increased from 2 to 14 microM, Km for UTP decreased from 126 to 50 microM, and Vmax increased 12-fold from 0.2 to 2.3 nmol/mg/min. Northern blot analyses of polyadenylated RNA from the resistant and sensitive cells indicated a 3-fold increase in transcripts of the CTP synthase gene in the resistant line. Consistent with these alterations in the properties of the enzyme, the resistant cells exhibited significantly expanded CTP and dCTP pools (4- 5-fold) when compared with the sensitive cells. No change was observed, however, in the properties of uridine-cytidine kinase, the enzyme responsible for the initial phosphorylation of CPEC; despite this, however, cellular uptake of CPEC was greatly decreased, and phosphorylation of CPEC and its incorporation into RNA were 10-fold less than in the parental cells. These latter observations are most readily explained by feedback inhibition by the increased CTP levels of the resistant cells of uridine-cytidine kinase and/or of the membrane transport process used for initial entry of CPEC. PMID:7694793

Zhang, H; Cooney, D A; Zhang, M H; Ahluwalia, G; Ford, H; Johns, D G

1993-12-01

404

Insights into Gene Expression Changes Impacting B-Cell Transformation: Cross-Species Microarray Analysis of Bovine Leukemia Virus Tax-Responsive Genes in Ovine B Cells  

Microsoft Academic Search

Large-animal models for leukemia have the potential to aid in the understanding of networks that contribute to oncogenesis. Infection of cattle and sheep with bovine leukemia virus (BLV), a complex retrovirus related to human T-cell leukemia virus type 1 (HTLV-1), is associated with the development of B-cell leukemia. Whereas the natural disease in cattle is characterized by a low tumor

Pavel Klener; Maud Szynal; Yvette Cleuter; Makram Merimi; Hugues Duvillier; Francoise Lallemand; Claude Bagnis; Philip Griebel; Christos Sotiriou; Arsene Burny; Philippe Martiat; Anne Van den Broeke

2006-01-01

405

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

2014-03-12

406

Clonal selection in xenografted human T cell acute lymphoblastic leukemia recapitulates gain of malignancy at relapse  

PubMed Central

Genomic studies in human acute lymphoblastic leukemia (ALL) have revealed clonal heterogeneity at diagnosis and clonal evolution at relapse. In this study, we used genome-wide profiling to compare human T cell ALL samples at the time of diagnosis and after engraftment (xenograft) into immunodeficient recipient mice. Compared with paired diagnosis samples, the xenograft leukemia often contained additional genomic lesions in established human oncogenes and/or tumor suppressor genes. Mimicking such genomic lesions by short hairpin RNA–mediated knockdown in diagnosis samples conferred a selective advantage in competitive engraftment experiments, demonstrating that additional lesions can be drivers of increased leukemia-initiating activity. In addition, the xenograft leukemias appeared to arise from minor subclones existing in the patient at diagnosis. Comparison of paired diagnosis and relapse samples showed that, with regard to genetic lesions, xenograft leukemias more frequently more closely resembled relapse samples than bulk diagnosis samples. Moreover, a cell cycle– and mitosis-associated gene expression signature was present in xenograft and relapse samples, and xenograft leukemia exhibited diminished sensitivity to drugs. Thus, the establishment of human leukemia in immunodeficient mice selects and expands a more aggressive malignancy, recapitulating the process of relapse in patients. These findings may contribute to the design of novel strategies to prevent or treat relapse.

Clappier, Emmanuelle; Gerby, Bastien; Sigaux, Francois; Delord, Marc; Touzri, Farah; Hernandez, Lucie; Ballerini, Paola; Baruchel, Andre

2011-01-01

407

Killer cell immunoglobulin-like receptors in Thai patients with leukemia and diffuse large B-cell lymphoma.  

PubMed

Natural killer (NK) cells are key components of the innate immune system that have been implicated in the immune response against tumor cells. Killer cell immunoglobulin-like receptors (KIR) regulate NK cell activity by interaction with specific human leukocyte antigen (HLA) class I. In this study, KIR gene polymorphisms and their HLA ligands were investigated in Thai patients with chronic myelogenous leukemia (CML) (n=60), acute myelogenous leukemia (AML) (n=60), acute lymphoblastic leukemia (ALL) (n=55), and diffuse large B-cell lymphoma (DLBCL) (n=60) compared with 150 healthy controls. The frequency of KIR3DL1 with HLA-Bw4 was significantly lower in DLBCL patients than in controls (P=0.0006, Pc=0.02), whereas no significant differences were seen in KIR gene frequencies and their ligands between leukemia patients and controls. This study suggest a role of inhibitory KIR with its ligand in the protection against DLBCL. PMID:24755352

Vejbaesya, Sasijit; Sae-Tam, Pradermchai; Khuhapinant, Archrob; Srinak, Duangporn

2014-07-01

408

Ezrin dephosphorylation/downregulation contributes to ursolic acid-mediated cell death in human leukemia cells  

PubMed Central

Ezrin links the actin filaments with the cell membrane and has a functional role in the apoptotic process. It appears clear that ezrin is directly associated with Fas, leading to activation of caspase cascade and cell death. However, the exact role of ezrin in ursolic acid (UA)-induced apoptosis remains unclear. In this study, we show for the first time that UA induces apoptosis in both transformed and primary leukemia cells through dephosphorylation/downregulation of ezrin, association and polarized colocalization of Fas and ezrin, as well as formation of death-inducing signaling complex. These events are dependent on Rho-ROCK1 signaling pathway. Knockdown of ezrin enhanced cell death mediated by UA, whereas overexpression of ezrin attenuated UA-induced apoptosis. Our in vivo study also showed that UA-mediated inhibition of tumor growth of mouse leukemia xenograft model is in association with the dephosphorylation/downregulation of ezrin. Such findings suggest that the cytoskeletal protein ezrin may represent an attractive target for UA-mediated lethality in human leukemia cells.

Li, G; Zhou, T; Liu, L; Chen, J; Zhao, Z; Peng, Y; Li, P; Gao, N

2013-01-01

409

Cytogenetics in multiple myeloma and plasma cell leukemia: simultaneous cytogenetic and cytologic studies in 51 patients  

Microsoft Academic Search

Summary Cytogenetic studies in patients with multiple myeloma (MM) and plasma cell leukemia (PCL) have in general been largely unsuccessful. The investigation of mitoses of nonmalignant hematopoietic precursor cells, rather than mitoses of malignant plasma cells might account for the low percentage of pathological genetic findings. We investigated bone marrow (BM) cells of 51 patients both cytogenetically and cytologically. In

K. Gutensohn; H. J. Weh; T. A. Walter; D. K. Hossfeld

1992-01-01

410

Emerging Therapeutic Strategies for Targeting Chronic Myeloid Leukemia Stem Cells  

PubMed Central

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

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

2013-01-01

411

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

412

Construction and properties of retrovirus packaging cells based on gibbon ape leukemia virus.  

PubMed Central

We have constructed hybrid retrovirus packaging cell lines that express the gibbon ape leukemia virus env and the Moloney murine leukemia virus gag-pol proteins. These cells were used to produce a retrovirus vector at over 10(6) CFU/ml, with a host range that included rat, hamster, bovine, cat, dog, monkey, and human cells. The gag-pol and env expression plasmids were separately transfected to reduce the potential for helper virus production, which was not observed. The NIH 3T3 mouse cells from which the packaging lines were made are not infectable by gibbon ape leukemia virus; thus, the generation and spread of possible recombinant viruses in the packaging cells is greatly reduced. These simian virus-based packaging cells extend the host range of currently available murine and avian packaging cells and should be useful for efficient gene transfer into higher mammals.

Miller, A D; Garcia, J V; von Suhr, N; Lynch, C M; Wilson, C; Eiden, M V

1991-01-01

413

Rap1GAP alters leukemia cell differentiation, apoptosis and invasion in vitro.  

PubMed

Rap1GAP which regulates the GTP-GDP form switch of Rap1 is a member of the GTPase-activating protein (GAP) family and has recently received substantial attention. Rap1GAP is thought of as a putative tumor suppressor gene and plays an important role in human tumor progression including pancreatic cancer, thyroid cancer and melanoma. In the current study, we found that the expression of Rap1GAP was lower in acute myeloid leukemia (AML) patients compared to non-malignant blood disease patients. The expression of Rap1GAP was also low in HL-60, NB4, U937 and SHI-1 myeloid leukemia cell lines. Upregulated Rap1GAP in NB4 and HL-60 cells promoted cell differentiation induced by ATRA or TPA compared to the empty vector control cells. Furthermore, Rap1GAP-transfected cells also showed a higher rate of apoptosis in response to arsenic trioxide compared to the control counterpart cells. In addition, we found that increased expression of Rap1GAP promoted leukemia cell invasion may be due to matrix metalloproteinase 9 (MMP9). In conclusion, these results demonstrated that Rap1GAP promoted leukemia cell differentiation and apoptosis, but increased leukemia cell invasion in vitro. PMID:22614916

Qiu, Tingting; Qi, Xiaofei; Cen, Jiannong; Chen, Zixing

2012-08-01

414

Functional inhibition of osteoblastic cells in an in vivo mouse model of myeloid leukemia  

PubMed Central

Pancytopenia is a major cause of morbidity in acute myeloid leukemia (AML), yet its cause is unclear. Normal osteoblastic cells have been shown to support hematopoiesis. To define the effects of leukemia on osteoblastic cells, we used an immunocompetent murine model of AML. Leukemic mice had inhibition of osteoblastic cells, with decreased serum levels of the bone formation marker osteocalcin. Osteoprogenitor cells and endosteal-lining osteopontin+ cells were reduced, and osteocalcin mRNA in CD45? marrow cells was diminished. This resulted in severe loss of mineralized bone. Osteoclasts were only transiently increased without significant increases in bone resorption, and their inhibition only partially rescued leukemia-induced bone loss. In vitro data suggested that a leukemia-derived secreted factor inhibited osteoblastic cells. Because the chemokine CCL-3 was recently reported to inhibit osteoblastic function in myeloma, we tested its expression in our model and in AML patients. Consistent with its potential novel role in leukemic-dependent bone loss, CCL-3 mRNA was significantly increased in malignant marrow cells from leukemic mice and from samples from AML patients. Based on these results, we propose that therapeutic mitigation of leukemia-induced uncoupling of osteoblastic and osteoclastic cells may represent a novel approach to promote normal hematopoiesis in patients with myeloid neoplasms.

Frisch, Benjamin J.; Ashton, John M.; Xing, Lianping; Becker, Michael W.; Jordan, Craig T.

2012-01-01

415

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.

Geng, Chuan-dong; Vedeckis, Wayne V.

2010-01-01

416

Stromal-mediated protection of tyrosine kinase inhibitor-treated BCR-ABL-expressing leukemia cells  

PubMed Central

Clinical studies of patients with chronic myeloid leukemia (CML) revealed that a common pattern of response is a dramatic fall in the circulating population of blast cells, with a minimal or delayed decrease in marrow blasts, suggesting a protective environment. These observations suggest that a greater understanding of the interaction of stromal cells with leukemic cells is essential. Here, we present an in vivo system for monitoring relative tumor accumulation in leukemic mice and residual disease in leukemic mice treated with a tyrosine kinase inhibitor, and an in vitro system for identifying integral factors involved in stromal-mediated cytoprotection. Using the in vivo model, we observed high tumor burden/residual disease in tissues characterized as significant sources of hematopoiesis-promoting stroma, with bone marrow stroma most frequently showing the highest accumulation of leukemia in untreated and nilotinib-treated mice, as well as partial protection of leukemic cells from the inhibitory effects of nilotinib. These studies, which showed a pattern of leukemia distribution consistent with what is observed in imatinib- and nilotinib-treated CML patients, were followed by a more in-depth analysis of stroma-leukemia cell interactions that lead to protection of leukemia cells from nilotinib-induced cytotoxicity. For the latter, we used the human BCR-ABL-positive cell line, KU812F, and the human bone marrow stroma cell line, HS-5, to more closely approximate the bone marrow-associated cytoprotection observed in drug-treated leukemia patients. This in vitro system helped to elucidate stromal-secreted viability factors that may play a role in stromal-mediated cytoprotection of tyrosine kinase inhibitor-treated leukemia cells.

Weisberg, Ellen; Wright, Renee D.; McMillin, Douglas W.; Mitsiades, Constantine; Ray, Arghya; Barrett, Rosemary; Adamia, Sophia; Stone, Richard; Galinsky, Ilene; Kung, Andrew L.; Griffin, James D.

2014-01-01

417

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.

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

418

Cyclopamine induces eosinophilic differentiation and upregulates CD44 expression in myeloid leukemia cells.  

PubMed

Cyclopamine, a plant-derived steroidal alkaloid, inhibits the hedgehog (Hh) signaling pathway by antagonizing Smoothened. This drug can induce the differentiation of myeloid leukemia cell lines and acute myeloid leukemia (AML) cells in primary culture. The treated cells were stained with Luxol-fast-blue, which is specific for eosinophilic granules. Ligation of CD44 with some specific monoclonal antibodies can reverse the differentiation of AML cells. Combined treatment with cyclopamine and a monoclonal antibody to ligate CD44 more than additively induced the differentiation of HL-60 cells. These results may provide useful information for the development of a CD44-targeted therapy in AML. PMID:20971508

Takahashi, Tsutomu; Kawakami, Koshi; Mishima, Seiji; Akimoto, Miho; Takenaga, Keizo; Suzumiya, Junji; Honma, Yoshio

2011-05-01

419

Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells  

PubMed Central

RUNX1 is generally considered a tumor suppressor in myeloid neoplasms. Inactivating RUNX1 mutations have frequently been found in patients with myelodysplastic syndrome (MDS) and cytogenetically normal acute myeloid leukemia (AML). However, no somatic RUNX1 alteration was found in AMLs with leukemogenic fusion proteins, such as core-binding factor (CBF) leukemia and MLL fusion leukemia, raising the possibility that RUNX1 could actually promote the growth of these leukemia cells. Using normal human cord blood cells and those expressing leukemogenic fusion proteins, we discovered a dual role of RUNX1 in myeloid leukemogenesis. RUNX1 overexpression inhibited the growth of normal cord blood cells by inducing myeloid differentiation, whereas a certain level of RUNX1 activity was required for the growth of AML1-ETO and MLL-AF9 cells. Using a mouse genetic model, we also showed that the combined loss of Runx1/Cbfb inhibited leukemia development induced by MLL-AF9. RUNX2 could compensate for the loss of RUNX1. The survival effect of RUNX1 was mediated by BCL2 in MLL fusion leukemia. Our study unveiled an unexpected prosurvival role for RUNX1 in myeloid leukemogenesis. Inhibiting RUNX1 activity rather than enhancing it could be a promising therapeutic strategy for AMLs with leukemogenic fusion proteins.

Goyama, Susumu; Schibler, Janet; Cunningham, Lea; Zhang, Yue; Rao, Yalan; Nishimoto, Nahoko; Nakagawa, Masahiro; Olsson, Andre; Wunderlich, Mark; Link, Kevin A.; Mizukawa, Benjamin; Grimes, H. Leighton; Kurokawa, Mineo; Liu, P. Paul; Huang, Gang; Mulloy, James C.

2013-01-01

420

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

2013-09-03