scholarly journals Proliferation and cytogenetic analysis of hairy cell leukemia upon stimulation via the CD40 antigen

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3134-3141 ◽  
Author(s):  
HC Kluin-Nelemans ◽  
GC Beverstock ◽  
P Mollevanger ◽  
HW Wessels ◽  
E Hoogendoorn ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Cultured Cells ◽  
Thymidine Incorporation ◽  
Interleukin 4 ◽  
Soluble Form ◽  
Cross Linking ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
In Vitro Proliferation

Abstract Using the CD40 system, in vitro proliferation of hairy cell leukemia (HCL) was examined in 43 patients. In this culture system, cells were stimulated by interleukin-4 (IL-4) and anti-CD40 monoclonal antibodies (MoAbs) that were added in soluble form or were cross-linked via their Fc part using Fc gamma RII-transfected mouse fibroblast cells. Proliferation was induced and confirmed by 3H-thymidine incorporation in 14 cases and by the presence of metaphases in 42 cases. 3H-thymidine incorporation showed a heterogeneous pattern: cross-linking of anti- CD40 gave the highest proliferation in 8 cases; in 11 cases, stimulation with anti-CD40 MoAbs alone, without cross-linking also resulted in proliferation; the addition of IL-4 further enhanced 3H- thymidine incorporation in 5 cases, but suppressed this phenomenon in 5 other cases. The CD40 system proved to be very effective in obtaining cytogenetic data. With a success rate of 42 of 43 patients tested, we found clonal abnormalities in 8 cases (19%) and nonclonal abnormalities with involvement of one or two abnormal metaphases in another 7 cases. The chromosomes most frequently involved in the abnormal karyotypes, both structurally and numerically, were chromosomes 5, 7, and 14. By fluorescence-activated cell-sorting analysis of the cultured cells, and by immunophenotypic analysis of metaphase spreads, T-cell growth could be excluded and the HCL-lineage confirmed. Stimulation via the CD40 antigen is an excellent tool for growing hairy cell leukemia cells.

scholarly journals Proliferation and cytogenetic analysis of hairy cell leukemia upon stimulation via the CD40 antigen

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3134-3141 ◽  
Author(s):  
HC Kluin-Nelemans ◽  
GC Beverstock ◽  
P Mollevanger ◽  
HW Wessels ◽  
E Hoogendoorn ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Cultured Cells ◽  
Thymidine Incorporation ◽  
Interleukin 4 ◽  
Soluble Form ◽  
Cross Linking ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
In Vitro Proliferation

Using the CD40 system, in vitro proliferation of hairy cell leukemia (HCL) was examined in 43 patients. In this culture system, cells were stimulated by interleukin-4 (IL-4) and anti-CD40 monoclonal antibodies (MoAbs) that were added in soluble form or were cross-linked via their Fc part using Fc gamma RII-transfected mouse fibroblast cells. Proliferation was induced and confirmed by 3H-thymidine incorporation in 14 cases and by the presence of metaphases in 42 cases. 3H-thymidine incorporation showed a heterogeneous pattern: cross-linking of anti- CD40 gave the highest proliferation in 8 cases; in 11 cases, stimulation with anti-CD40 MoAbs alone, without cross-linking also resulted in proliferation; the addition of IL-4 further enhanced 3H- thymidine incorporation in 5 cases, but suppressed this phenomenon in 5 other cases. The CD40 system proved to be very effective in obtaining cytogenetic data. With a success rate of 42 of 43 patients tested, we found clonal abnormalities in 8 cases (19%) and nonclonal abnormalities with involvement of one or two abnormal metaphases in another 7 cases. The chromosomes most frequently involved in the abnormal karyotypes, both structurally and numerically, were chromosomes 5, 7, and 14. By fluorescence-activated cell-sorting analysis of the cultured cells, and by immunophenotypic analysis of metaphase spreads, T-cell growth could be excluded and the HCL-lineage confirmed. Stimulation via the CD40 antigen is an excellent tool for growing hairy cell leukemia cells.

Hairy cell leukemia: In-vitro proliferation and pseudo-colony formation

1987 ◽  
Vol 11 (10) ◽  
pp. 911-921 ◽  
Author(s):  
J.C. Kluin-Nelemans ◽  
H.W.J. Hakvoort ◽  
J.T. van Dissel ◽  
J.H. van Dierendonck ◽  
G.C. Beverstock ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Colony Formation ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
In Vitro Proliferation

scholarly journals Soluble interleukin-2 receptors in the sera of patients with hairy cell leukemia: relationship with the effect of recombinant alpha-interferon therapy on clinical parameters and natural killer in vitro activity

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1530-1535 ◽  
Author(s):  
M Chilosi ◽  
G Semenzato ◽  
G Cetto ◽  
A Ambrosetti ◽  
L Fiore-Donati ◽  
...  
Keyword(s):  
Natural Killer ◽  
Hairy Cell Leukemia ◽  
Interleukin 2 ◽  
Alpha Interferon ◽  
Soluble Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Mediated Immunity ◽  
Hairy Cell ◽  
Cell Leukemia

Abstract In this study we provide evidence that the sera of patients with hairy cell leukemia (HCL) contain a factor that can prevent the binding of a monoclonal antibody specific for interleukin-2 receptor (IL-2R) to its target. This factor corresponds to the soluble form of IL-2R (sIL-2R), as assessed by a specific enzyme-linked immunosorbent assay test, and appears to be released by neoplastic hairy cells. The serum sIL-2R levels were very high at diagnosis and significantly reduced during recombinant alpha-interferon (rIFN alpha 2) therapy. Values of sIL-2R appeared to be inversely related to the natural killer in vitro function displayed by peripheral blood mononuclear cells from the same patients. The presence of sIL-2R in the serum of patients with HCL might be involved in the impairment of cell-mediated immunity observed in these patients and could represent a valuable marker for monitoring different phases of the disease and for modulating IFN therapy.

scholarly journals Soluble interleukin-2 receptors in the sera of patients with hairy cell leukemia: relationship with the effect of recombinant alpha-interferon therapy on clinical parameters and natural killer in vitro activity

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1530-1535
Author(s):  
M Chilosi ◽  
G Semenzato ◽  
G Cetto ◽  
A Ambrosetti ◽  
L Fiore-Donati ◽  
...  
Keyword(s):  
Natural Killer ◽  
Hairy Cell Leukemia ◽  
Interleukin 2 ◽  
Alpha Interferon ◽  
Soluble Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Mediated Immunity ◽  
Hairy Cell ◽  
Cell Leukemia

In this study we provide evidence that the sera of patients with hairy cell leukemia (HCL) contain a factor that can prevent the binding of a monoclonal antibody specific for interleukin-2 receptor (IL-2R) to its target. This factor corresponds to the soluble form of IL-2R (sIL-2R), as assessed by a specific enzyme-linked immunosorbent assay test, and appears to be released by neoplastic hairy cells. The serum sIL-2R levels were very high at diagnosis and significantly reduced during recombinant alpha-interferon (rIFN alpha 2) therapy. Values of sIL-2R appeared to be inversely related to the natural killer in vitro function displayed by peripheral blood mononuclear cells from the same patients. The presence of sIL-2R in the serum of patients with HCL might be involved in the impairment of cell-mediated immunity observed in these patients and could represent a valuable marker for monitoring different phases of the disease and for modulating IFN therapy.

scholarly journals Alterations in the phenotype of hairy cells during culture in the presence of PHA: requirement for T cells

Blood ◽  
1982 ◽  
Vol 59 (5) ◽  
pp. 895-899 ◽  
Author(s):  
CP Worman ◽  
PC Beverley ◽  
JC Cawley
Keyword(s):  
T Cells ◽  
Hairy Cell Leukemia ◽  
Mononuclear Cells ◽  
Cultured Cells ◽  
Phenotypic Change ◽  
Cell Contact ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Peripheral Blood Mononuclear ◽  
Hairy Cells

Abstract Culture studies of peripheral blood mononuclear cells from 7 entirely typical cases of hairy cell leukemia showed that after culture in the presence of PHA for 2--5 days, the predominant cell type changed from E- SIg+ CIg+ gamma FcR+ muFcR+ hairy cells to an E+ SIg- CIg- gamma FcR- muFcR- population of transformed cells derived from hairy cells. Depletion and readdition experiments demonstrated that cell-to-cell contact with T cells was necessary for the phenotypic change, while several observations indicated that the E+ population was not derived from T cells present before culture. The E positivity of the cultured cells was shown to be due to the possession of E receptor not acquired from the culture fluid, but the cells differed from true T cells in lacking both mature and immature T-cell antigens. The relevance of these in vitro observations to the continuing controversy concerning the nature of the hairy cell and to the in vivo fluctuations in immunologic phenotype not infrequently observed in hairy cell leukemia is briefly discussed.

scholarly journals In vivo induction of proteins during therapy of hairy cell leukemia with alpha-interferon

Blood ◽  
1987 ◽  
Vol 69 (6) ◽  
pp. 1570-1573 ◽  
Author(s):  
BL Samuels ◽  
HM Golomb ◽  
BH Brownstein
Keyword(s):  
Hairy Cell Leukemia ◽  
Polyacrylamide Gel Electrophoresis ◽  
Specific Protein ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Biochemical Effect ◽  
Ifn Alpha ◽  
Hairy Cells

Abstract The mechanism of the antineoplastic effect of interferon (IFN) is not known and may result from direct effects on the neoplastic cells themselves, activation of intermediary effector cells, or a combination of these effects. The synthesis of specific proteins is induced in hairy cells when they are exposed to alpha-IFN in vitro. In particular, the called p80, is markedly induced. We investigated this effect in the hairy cells of seven patients in the leukemic phase of hairy cell leukemia who were being treated with subcutaneous (SC) IFN alpha 2b (r- Hu-IFN-alpha 2). Polyacrylamide gel electrophoresis (PAGE) was carried out on [35S]methionine-labeled whole cell lysates visualized by autoradiography and silver staining. Within 2 days of starting IFN therapy, induction of specific protein synthesis, including p80 was seen by [35S]methionine labeling in freshly isolated circulating hairy cells from 6 of 6 patients tested. Therefore, alpha-IFN has a direct biochemical effect on hairy cells in vivo that is similar to in vitro effects, at least with regard to p80 synthesis, although the kinetics of this effect may vary in the two situations.

scholarly journals Serum soluble IL-2 receptor as a tumor marker in patients with hairy cell leukemia

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1304-1309 ◽  
Author(s):  
RG Steis ◽  
L Marcon ◽  
J Clark ◽  
W Urba ◽  
DL Longo ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Interferon Alpha ◽  
Hairy Cell Leukemia ◽  
Interleukin 2 ◽  
Response To Therapy ◽  
Soluble Form ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Activated T Cells ◽  
Recombinant Interferon

Abstract Activated T cells synthesize and express a cell membrane-bound receptor for interleukin-2 (IL-2) and have recently been shown to secrete a soluble form of the same receptor. Hairy cell leukemia is a chronic disorder caused by expansion of a clonal population of an unusual mononuclear cell of B cell origin. These cells have previously been shown to express an IL-2 receptor on the cell membrane. The sera of 26 patients with hairy cell leukemia were examined for the presence of a soluble IL-2 receptor before and during therapy with either recombinant interferon alpha-2a or 2′-deoxycoformycin. Before therapy, all patients had markedly elevated levels of this soluble IL-2 receptor ranging from five to 60 times the highest level observed in normal control sera. In individual patients changes in the level during therapy correlated well with clinical assessments of tumor response; levels fell to near the normal range in patients responding to therapy. Patients not responding to interferon alpha had no significant change in the soluble IL-2 receptor level. These results suggest that hairy cells secrete a soluble IL-2 receptor and that serial measurements of the level of this receptor in the serum can be used as a noninvasive means to assess disease response to therapy.

scholarly journals In Vitro Sensitivity to Venetoclax and Microenvironment Protection in Hairy Cell Leukemia

2021 ◽  
Vol 11 ◽  
Author(s):  
Alexia Vereertbrugghen ◽  
Ana Colado ◽  
Ernesto Gargiulo ◽  
Raimundo Fernando Bezares ◽  
Horacio Fernández Grecco ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Annexin V ◽  
The Elderly ◽  
Lymphocytic Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Current Standard ◽  
Activated T Lymphocytes ◽  
Low Incidence

Current standard treatment of patients with hairy cell leukemia (HCL), a chronic B-cell neoplasia of low incidence that affects the elderly, is based on the administration of purine analogs such as cladribine. This chemotherapy approach shows satisfactory responses, but the disease relapses, often repeatedly. Venetoclax (ABT-199) is a Bcl-2 inhibitor currently approved for the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) in adult patients ineligible for intensive chemotherapy. Given that HCL cells express Bcl-2, our aim was to evaluate venetoclax as a potential therapy for HCL. We found that clinically relevant concentrations of venetoclax (0.1 and 1 µM) induced primary HCL cell apoptosis in vitro as measured by flow cytometry using Annexin V staining. As microenvironment induces resistance to venetoclax in CLL, we also evaluated its effect in HCL by testing the following stimuli: activated T lymphocytes, stromal cells, TLR-9 agonist CpG, and TLR-2 agonist PAM3. We found decreased levels of venetoclax-induced cytotoxicity in HCL cells exposed for 48 h to any of these stimuli, suggesting that leukemic B cells from HCL patients are sensitive to venetoclax, but this sensitivity can be overcome by signals from the microenvironment. We propose that the combination of venetoclax with drugs that target the microenvironment might improve its efficacy in HCL.

scholarly journals Alterations in the phenotype of hairy cells during culture in the presence of PHA: requirement for T cells

Blood ◽  
1982 ◽  
Vol 59 (5) ◽  
pp. 895-899 ◽  
Author(s):  
CP Worman ◽  
PC Beverley ◽  
JC Cawley
Keyword(s):  
T Cells ◽  
Hairy Cell Leukemia ◽  
Mononuclear Cells ◽  
Cultured Cells ◽  
Phenotypic Change ◽  
Cell Contact ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Peripheral Blood Mononuclear ◽  
Hairy Cells

Culture studies of peripheral blood mononuclear cells from 7 entirely typical cases of hairy cell leukemia showed that after culture in the presence of PHA for 2--5 days, the predominant cell type changed from E- SIg+ CIg+ gamma FcR+ muFcR+ hairy cells to an E+ SIg- CIg- gamma FcR- muFcR- population of transformed cells derived from hairy cells. Depletion and readdition experiments demonstrated that cell-to-cell contact with T cells was necessary for the phenotypic change, while several observations indicated that the E+ population was not derived from T cells present before culture. The E positivity of the cultured cells was shown to be due to the possession of E receptor not acquired from the culture fluid, but the cells differed from true T cells in lacking both mature and immature T-cell antigens. The relevance of these in vitro observations to the continuing controversy concerning the nature of the hairy cell and to the in vivo fluctuations in immunologic phenotype not infrequently observed in hairy cell leukemia is briefly discussed.

scholarly journals Host defense deficiency in hairy cell leukemia and its correction by leukocyte transfusion

Blood ◽  
1980 ◽  
Vol 56 (3) ◽  
pp. 526-533 ◽  
Author(s):  
EM Hersh ◽  
S Murphy ◽  
A Zander ◽  
K Dicke ◽  
DJ Stewart ◽  
...  
Keyword(s):  
Host Defense ◽  
Hairy Cell Leukemia ◽  
Defense Mechanisms ◽  
Pokeweed Mitogen ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Con A ◽  
Dependent Cell ◽  
Monocyte Adherence

Abstract A similar defect host defense mechanisms in hairy cell leukemia was defined in two patients. Surface-adherent monocytes were not detected in the peripheral blood nor were monocytes that mediate antibody- dependent cell-mediated cytotoxicity (ADCC) to isoantibody-coated human erythrocytes. In addition, lymphocytes of both patients failed to show blastogenic responses to concanavalin A (Con-A) and pokeweed mitogen (PWM) but showed a vigorous response to phytohemagglutinin (PHA). Other immunologic abnormalities were present but were either moderate in degree or were not present in both patients. In vitro lymphocyte blastogenic responses were fully restored by incubation of patients' leukocytes with a normal donor's adherent monocytes. One patient received daily allogeneic leukocyte transfusion for 4 days. This resulted in complete normalization of monocyte adherence and ADCC that persisted for several months after transfusion and was associated with hemotalogic improvement. Therapy in case 1 resulted in correction of the blastogenic responses to Con-A and PWM. Thus, a host defense defect in hairy cell leukemia has been defined in 2 patients and a preliminary result suggests that therapy with leukocyte transfusions may be useful in the postsplenectomy patient with an infectious complication and should be explored further.

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