scholarly journals Response patterns of hairy cell leukemia to B-cell mitogens and growth factors

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 2091-2097
Author(s):  
BA Barut ◽  
MK Cochran ◽  
C O'Hara ◽  
KC Anderson
Keyword(s):  
Growth Factors ◽  
Dna Synthesis ◽  
B Cell ◽  
Tumor Cells ◽  
Hairy Cell Leukemia ◽  
Proliferative Response ◽  
Tartrate Resistant Acid Phosphatase ◽  
Hairy Cell ◽  
Cell Leukemia

The effect of mitogens and/or recombinant B-cell growth factors (M/GFs) on the in vitro growth of hairy cells was examined. Tumor cells were isolated from the spleens of four patients with hairy cell leukemia (HCL) by Ficoll-Hypaque sedimentation and E-rosetting. Enrichment for tumor cells was confirmed with intracytoplasmic immunoglobulin (Ig) staining, tartrate resistant acid phosphatase (TRAP) staining, and staining using monoclonal antibodies (MoAbs) directed at B, T, myeloid, and monocytoid antigens (Ags) in indirect immunofluorescence assays. Tumor cells were B1(CD20)+ B2(CD21)- B4(CD19)+ IL-2R(CD25)+ PCA-1 +/- TRAP+. HCLs neither synthesized DNA nor secreted Ig in response to culture with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, or IL-6. However, a proliferative response (stimulation index greater than or equal to 3.0) without Ig secretion was triggered in HCLs by mitogens or combinations of GFs. Specifically, DNA synthesis was induced at 3 days in three of four HCL samples cultured with Staphylococcus aureus Cowan A (SAC) or the combination of phorbol ester (TPA) and the calcium ionophore A 23187 (Ca2+); DNA synthesis was triggered later (day 7) by tumor necrosis factor (TNF) or by IL-4 and IL-5. In contrast, the fourth patient, a nonresponder to SAC or TPA/Ca2+, demonstrated increased DNA synthesis at day 3 when cocultured with IL-4 and IL-5. Both autoradiography and staining with antibromodeoxyuridine (BrdU) MoAb conjugated to fluorescein confirmed DNA synthesis by only a minority (5% to 23%) of tumor cells within each patient. Dual staining confirmed that responsive cells were both BrdU+ and TRAP+. DNA synthesis induced by TPA/Ca2+ was blocked specifically by anti-IL-6 Ab; in contrast, the HCL proliferative response to SAC, TNF, or IL-4 and IL- 5 was not inhibited by anti-IL-6 Ab. alpha-Interferon inhibited the response to TPA/Ca2+, TNF, or IL-4 and IL-5 without any effect on response to SAC. Finally, peroxidase-antiperoxidase staining demonstrated that HCLs are induced by TPA/Ca2+, but not by SAC, to produce intracytoplasmic IL-6. These data demonstrate IL-4, IL-5, and IL-6 mediated DNA synthesis by HCLs in vitro and suggest a possible in vivo role for these growth factors in the pathophysiology of HCL.

scholarly journals Response patterns of hairy cell leukemia to B-cell mitogens and growth factors

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 2091-2097 ◽  
Author(s):  
BA Barut ◽  
MK Cochran ◽  
C O'Hara ◽  
KC Anderson
Keyword(s):  
Growth Factors ◽  
Dna Synthesis ◽  
B Cell ◽  
Tumor Cells ◽  
Hairy Cell Leukemia ◽  
Proliferative Response ◽  
Tartrate Resistant Acid Phosphatase ◽  
Hairy Cell ◽  
Cell Leukemia

Abstract The effect of mitogens and/or recombinant B-cell growth factors (M/GFs) on the in vitro growth of hairy cells was examined. Tumor cells were isolated from the spleens of four patients with hairy cell leukemia (HCL) by Ficoll-Hypaque sedimentation and E-rosetting. Enrichment for tumor cells was confirmed with intracytoplasmic immunoglobulin (Ig) staining, tartrate resistant acid phosphatase (TRAP) staining, and staining using monoclonal antibodies (MoAbs) directed at B, T, myeloid, and monocytoid antigens (Ags) in indirect immunofluorescence assays. Tumor cells were B1(CD20)+ B2(CD21)- B4(CD19)+ IL-2R(CD25)+ PCA-1 +/- TRAP+. HCLs neither synthesized DNA nor secreted Ig in response to culture with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, or IL-6. However, a proliferative response (stimulation index greater than or equal to 3.0) without Ig secretion was triggered in HCLs by mitogens or combinations of GFs. Specifically, DNA synthesis was induced at 3 days in three of four HCL samples cultured with Staphylococcus aureus Cowan A (SAC) or the combination of phorbol ester (TPA) and the calcium ionophore A 23187 (Ca2+); DNA synthesis was triggered later (day 7) by tumor necrosis factor (TNF) or by IL-4 and IL-5. In contrast, the fourth patient, a nonresponder to SAC or TPA/Ca2+, demonstrated increased DNA synthesis at day 3 when cocultured with IL-4 and IL-5. Both autoradiography and staining with antibromodeoxyuridine (BrdU) MoAb conjugated to fluorescein confirmed DNA synthesis by only a minority (5% to 23%) of tumor cells within each patient. Dual staining confirmed that responsive cells were both BrdU+ and TRAP+. DNA synthesis induced by TPA/Ca2+ was blocked specifically by anti-IL-6 Ab; in contrast, the HCL proliferative response to SAC, TNF, or IL-4 and IL- 5 was not inhibited by anti-IL-6 Ab. alpha-Interferon inhibited the response to TPA/Ca2+, TNF, or IL-4 and IL-5 without any effect on response to SAC. Finally, peroxidase-antiperoxidase staining demonstrated that HCLs are induced by TPA/Ca2+, but not by SAC, to produce intracytoplasmic IL-6. These data demonstrate IL-4, IL-5, and IL-6 mediated DNA synthesis by HCLs in vitro and suggest a possible in vivo role for these growth factors in the pathophysiology of HCL.

scholarly journals Hairy cell leukemia: a tumor of pre-plasma cells

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 620-629 ◽  
Author(s):  
KC Anderson ◽  
AW Boyd ◽  
DC Fisher ◽  
D Leslie ◽  
SF Schlossman ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Plasma Cell ◽  
Hairy Cell Leukemia ◽  
Plasma Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Cell Surface Antigens ◽  
Hairy Cells

Monoclonal antibodies defining B-, T-, and myeloid-restricted cell surface antigens were used to characterize the lineage and state of differentiation of tumor cells isolated from 22 patients with hairy cell leukemia (HCL). These tumors were shown to be of B lineage because they strongly expressed the B cell-restricted antigens B1 and B4 and lacked T cell- and monocyte-restricted antigens. Moreover, the strong expression of the plasma cell-associated PCA-1 antigen on the majority of hairy cells suggested that these tumors correspond to later stages of B cell ontogeny. Dual fluorescence experiments further confirmed that HCL splenocytes that coexpressed B1 and PCA-1 demonstrated both the morphology and tartrate-resistant acid phosphatase positivity of hairy cells. The observation that some hairy cells either spontaneously produce immunoglobulin (Ig) or could be induced to proliferate and secrete Ig provides complementary support for the view that HCL is a pre-plasma cell tumor. However, staining of hairy cells with anti-IL2R1 monoclonal antibody, which is directed to the T cell growth factor receptor and/or with the anti-Mo1 reagent, directed to C3bi complement receptor, distinguish these cells from currently identified B cells.

scholarly journals Polyclonal B-Cell Lymphocytosis With Features Resembling Hairy Cell Leukemia-Japanese Variant

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 2008-2014 ◽  
Author(s):  
Takashi Machii ◽  
Mitsuhiro Yamaguchi ◽  
Ryoichi Inoue ◽  
Yukihiro Tokumine ◽  
Hirohiko Kuratsune ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Leukemia Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Variant Form ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Persistent Lymphocytosis ◽  
Biopsy Specimens

Abstract Polyclonal B lymphocytosis was found in four patients having clinical and hematologic features resembling those of hairy cell leukemia (HCL). All four patients were women between 37 and 67 years of age. Three patients had splenomegaly. Lymphadenopthy was absent or slight. Persistent lymphocytosis was seen in all the patients, and anemia and/or thrombopenia was observed in three of the patients. Abnormal lymphocytes have long microvilli and prominent membranous ruffles on their surfaces. Bone marrow aspirates and biopsy specimens showed increased numbers of abnormal lymphocytes with round nuclei and abundant pale cytoplasm. Although these findings were similar to those of HCL, studies of Ig gene rearrangements and expression showed the polyclonal proliferation of B cells. We called this new disease hairy B-cell lymphoproliferative disorder (HBLD). All four patients exhibited a polyclonal increase in serum IgG. The morphology of the cells in HBLD was more similar to that of leukemia cells of a variant form of HCL (HCL-Japanese variant) than to typical HCL cells. The surface IgG+, CD5−, CD11c+, CD22+, CD24−, CD25− phenotype and the weak tartrate-resistant acid phosphatase activity in the cells were identical to those of HCL cells of the Japanese variant. Our findings suggest that the B cells in HBLD are the nonmalignant counterpart of leukemic B cells in HCL-Japanese variant.

scholarly journals Diversity in inhibitory effects of IFN-gamma and IFN-alpha A on the induced DNA synthesis of a hairy cell leukemia B lymphocyte clone reflects the nature of the activating ligand

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1553-1559
Author(s):  
P Mongini ◽  
S Seremetis ◽  
C Blessinger ◽  
S Rudich ◽  
R Winchester ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Therapeutic Potential ◽  
Cell Clone ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Ifn Gamma ◽  
Recombinant Interferon ◽  
Ifn Alpha

A hairy cell leukemia population was used as a clonal model for studying the direct immunomodulatory effects of recombinant interferon- alpha A (rIFN-alpha A) and rIFN-gamma on human B-cell proliferation. The leukemic cell population KON was notably quiescent when incubated in medium alone but was induced to significant in vitro DNA synthesis when cultured with any of four activators of human B cells: anti-IgM antibody, Staphylococcus aureus cells (SAC), phorbol myristate acetate (PMA), or B-cell growth factor (BCGF). While both rIFN-gamma and rIFN- alpha A exhibited suppressive effects on these responses, their inhibitory patterns were distinct and reciprocal. Thus, rIFN-gamma exclusively suppressed anti-IgM-and SAC-induced leukemic DNA synthesis, and rIFN-alpha A significantly suppressed only PMA- and BCGF-induced DNA synthesis. The effects of the rIFN preparations were ablated in the presence of IFN type-specific monoclonal antibodies. Kinetic analyses and pulsing studies revealed that inhibition was most notable when cells were exposed concomitantly to IFN and the activating ligand. That the diverse effects of IFN-gamma and IFN-alpha A are manifested on a single B-cell clone was confirmed by Southern blot analysis of restriction enzyme-digested KON cell DNA with a JH-specific probe. These studies suggest that the therapeutic potential of the two types of IFN may be influenced by the nature of the extracellular ligands in the leukemic mileau that promote leukemic clonal expansion.

scholarly journals CD11c (LEU-M5) expression characterizes a B-cell chronic lymphoproliferative disorder with features of both chronic lymphocytic leukemia and hairy cell leukemia [see comments]

Blood ◽  
1990 ◽  
Vol 76 (11) ◽  
pp. 2360-2367
Author(s):  
CA Hanson ◽  
TE Gribbin ◽  
B Schnitzer ◽  
JA Schlegelmilch ◽  
BS Mitchell ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Lymphoproliferative Disorder ◽  
Cellular Adhesion ◽  
Lymphocytic Leukemia ◽  
Tartrate Resistant Acid Phosphatase ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Bone Marrow Biopsies

Chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL) are two common chronic lymphoproliferative disorders, each having characteristic clinical, morphologic, and immunologic features. Phenotypically, CD5 reactivity in CLL and CD11c (Leu-M5) reactivity in HCL have characterized these two leukemias among B-cell disorders. In this study, we report 14 cases of a novel chronic lymphoproliferative disorder characterized by lymphocytosis and CD11c expression, but morphologically similar to CLL. The patients' ages ranged from 46 to 81 years (median 62). Eleven had palpable splenomegaly, five with markedly enlarged spleens; only one patient had generalized lymphadenopathy. The white blood cell count ranged from 5.2 to 131.0 x 10(9)/L (median 20.8). The morphologic diagnosis in all cases was CLL, with the cells usually having abundant cytoplasm. No morphologic features, of hairy cells were evident; tartrate-resistant acid phosphatase cytochemistry was negative in all cases. Bone marrow biopsies were available in 8 of 14. Four showed focal nodular infiltrates and two had diffuse infiltrates similar to CLL; two showed only minimal interstitial involvement. All cases expressed multiple B-cell markers, and 12 of 14 had monoclonal surface immunoglobulin. The leukemic cells of all cases strongly expressed CD11c, while CD5 was expressed in 7 of 14; only 1 of the 14 cases expressed the lymph node homing receptor, Leu-8. This unique group of leukemias appears to represent the malignant transformation of lymphocytes arising from a stage of lymphocyte differentiation between that found in typical cases of CLL and that of HCL. CD11c is known to have an important function in cellular adhesion and may be important in determining the pattern of lymphocyte tissue distribution found in this group of patients.

scholarly journals CD11c (LEU-M5) expression characterizes a B-cell chronic lymphoproliferative disorder with features of both chronic lymphocytic leukemia and hairy cell leukemia [see comments]

Blood ◽  
1990 ◽  
Vol 76 (11) ◽  
pp. 2360-2367 ◽  
Author(s):  
CA Hanson ◽  
TE Gribbin ◽  
B Schnitzer ◽  
JA Schlegelmilch ◽  
BS Mitchell ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Lymphoproliferative Disorder ◽  
Cellular Adhesion ◽  
Lymphocytic Leukemia ◽  
Tartrate Resistant Acid Phosphatase ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Bone Marrow Biopsies

Abstract Chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL) are two common chronic lymphoproliferative disorders, each having characteristic clinical, morphologic, and immunologic features. Phenotypically, CD5 reactivity in CLL and CD11c (Leu-M5) reactivity in HCL have characterized these two leukemias among B-cell disorders. In this study, we report 14 cases of a novel chronic lymphoproliferative disorder characterized by lymphocytosis and CD11c expression, but morphologically similar to CLL. The patients' ages ranged from 46 to 81 years (median 62). Eleven had palpable splenomegaly, five with markedly enlarged spleens; only one patient had generalized lymphadenopathy. The white blood cell count ranged from 5.2 to 131.0 x 10(9)/L (median 20.8). The morphologic diagnosis in all cases was CLL, with the cells usually having abundant cytoplasm. No morphologic features, of hairy cells were evident; tartrate-resistant acid phosphatase cytochemistry was negative in all cases. Bone marrow biopsies were available in 8 of 14. Four showed focal nodular infiltrates and two had diffuse infiltrates similar to CLL; two showed only minimal interstitial involvement. All cases expressed multiple B-cell markers, and 12 of 14 had monoclonal surface immunoglobulin. The leukemic cells of all cases strongly expressed CD11c, while CD5 was expressed in 7 of 14; only 1 of the 14 cases expressed the lymph node homing receptor, Leu-8. This unique group of leukemias appears to represent the malignant transformation of lymphocytes arising from a stage of lymphocyte differentiation between that found in typical cases of CLL and that of HCL. CD11c is known to have an important function in cellular adhesion and may be important in determining the pattern of lymphocyte tissue distribution found in this group of patients.

scholarly journals Lack of T cell antigen expression on hairy cells of B cell origin after in vitro exposure to PHA

Blood ◽  
1984 ◽  
Vol 63 (4) ◽  
pp. 958-964 ◽  
Author(s):  
T Han ◽  
B Dadey ◽  
C Pollard ◽  
M Barcos ◽  
ML Bloom ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Antigen Expression ◽  
Cell Phenotype ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
In Vitro Exposure ◽  
Hairy Cells

Abstract The malignant monoclonal population in hairy cell leukemia (HCL) has been variously ascribed to be of myeloid, B, or even T cell origin. Recent data have been interpreted as suggesting that hairy cells (HC) may concomitantly or serially express both B and T surface determinants, a phenomenon which, if verified, would be unique among the lymphoproliferative malignancies. Data described here, however, demonstrate that (1) at least the majority of HCL are phenotypically of B cell derivation, and (2) the initial B cell phenotype is retained and solely expressed on cultured as well as phytohemagglutinin (PHA) activated monoclonal malignant HC.

scholarly journals Hairy cell leukemia: a tumor of pre-plasma cells

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 620-629 ◽  
Author(s):  
KC Anderson ◽  
AW Boyd ◽  
DC Fisher ◽  
D Leslie ◽  
SF Schlossman ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Plasma Cell ◽  
Hairy Cell Leukemia ◽  
Plasma Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Cell Surface Antigens ◽  
Hairy Cells

Abstract Monoclonal antibodies defining B-, T-, and myeloid-restricted cell surface antigens were used to characterize the lineage and state of differentiation of tumor cells isolated from 22 patients with hairy cell leukemia (HCL). These tumors were shown to be of B lineage because they strongly expressed the B cell-restricted antigens B1 and B4 and lacked T cell- and monocyte-restricted antigens. Moreover, the strong expression of the plasma cell-associated PCA-1 antigen on the majority of hairy cells suggested that these tumors correspond to later stages of B cell ontogeny. Dual fluorescence experiments further confirmed that HCL splenocytes that coexpressed B1 and PCA-1 demonstrated both the morphology and tartrate-resistant acid phosphatase positivity of hairy cells. The observation that some hairy cells either spontaneously produce immunoglobulin (Ig) or could be induced to proliferate and secrete Ig provides complementary support for the view that HCL is a pre-plasma cell tumor. However, staining of hairy cells with anti-IL2R1 monoclonal antibody, which is directed to the T cell growth factor receptor and/or with the anti-Mo1 reagent, directed to C3bi complement receptor, distinguish these cells from currently identified B cells.

scholarly journals Lack of T cell antigen expression on hairy cells of B cell origin after in vitro exposure to PHA

Blood ◽  
1984 ◽  
Vol 63 (4) ◽  
pp. 958-964
Author(s):  
T Han ◽  
B Dadey ◽  
C Pollard ◽  
M Barcos ◽  
ML Bloom ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Antigen Expression ◽  
Cell Phenotype ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
In Vitro Exposure ◽  
Hairy Cells

The malignant monoclonal population in hairy cell leukemia (HCL) has been variously ascribed to be of myeloid, B, or even T cell origin. Recent data have been interpreted as suggesting that hairy cells (HC) may concomitantly or serially express both B and T surface determinants, a phenomenon which, if verified, would be unique among the lymphoproliferative malignancies. Data described here, however, demonstrate that (1) at least the majority of HCL are phenotypically of B cell derivation, and (2) the initial B cell phenotype is retained and solely expressed on cultured as well as phytohemagglutinin (PHA) activated monoclonal malignant HC.

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