scholarly journals Rearrangement of both immunoglobulin and T-cell receptor genes in a prolymphocytic variant of hairy cell leukemia patient resistant to interferon-alpha [published erratum appears in Blood 1989 Feb;73(2):624]

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1708-1716
Author(s):  
SL Giardina ◽  
HA Young ◽  
CR Faltynek ◽  
ES Jaffe ◽  
JW Clark ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Peripheral Blood ◽  
Hairy Cell Leukemia ◽  
Cell Receptor ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Ifn Gamma ◽  
Ifn Alpha ◽  
Alpha Receptors

We describe a patient with the so-called “prolymphocytic variant” form of hairy cell leukemia (HCL) resistant to treatment with interferon- alpha (IFN-alpha). Analysis of immunoglobulin (Ig) and T-cell receptor- beta (TCR beta) gene rearrangements from serial peripheral blood mononuclear cell specimens (MNCs) confirmed not only the B-cell nature of the disease, but also the subsequent emergence of a morphologically indistinguishable population of cells with a clonal TCR beta rearrangement in addition to the original Ig gene rearrangement. With the exception of a transient increase in peripheral blood T cells during treatment with deoxycoformycin (DCF), the MNCs remained essentially constant throughout therapy with no evidence of a co- existing T-cell clone to account for the TCR beta rearrangement. Although MNCs from this patient bound significantly less IFN-alpha than did MNCs from other HCL patients, the binding was of high affinity with a kd similar to that of control cells. The number of IFN-gamma receptors on our patient's MNCs was four times higher than the number of IFN-alpha receptors and was similar to the number of IFN-alpha receptors on MNCs from HCL patients responsive to IFN-alpha. While various treatments including IFN-alpha, DCF, chlorambucil, splenectomy, leukopheresis, and IFN-gamma were not able to change the clinical progression of the disease, they may have provided an opportunity for the divergent TCR beta rearranged clone to expand and displace the initially dominant clone.

Rearrangement of both immunoglobulin and T-cell receptor genes in a prolymphocytic variant of hairy cell leukemia patient resistant to interferon-alpha [published erratum appears in Blood 1989 Feb;73(2):624]

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1708-1716 ◽  
Author(s):  
SL Giardina ◽  
HA Young ◽  
CR Faltynek ◽  
ES Jaffe ◽  
JW Clark ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Peripheral Blood ◽  
Hairy Cell Leukemia ◽  
Cell Receptor ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Ifn Gamma ◽  
Ifn Alpha ◽  
Alpha Receptors

Abstract We describe a patient with the so-called “prolymphocytic variant” form of hairy cell leukemia (HCL) resistant to treatment with interferon- alpha (IFN-alpha). Analysis of immunoglobulin (Ig) and T-cell receptor- beta (TCR beta) gene rearrangements from serial peripheral blood mononuclear cell specimens (MNCs) confirmed not only the B-cell nature of the disease, but also the subsequent emergence of a morphologically indistinguishable population of cells with a clonal TCR beta rearrangement in addition to the original Ig gene rearrangement. With the exception of a transient increase in peripheral blood T cells during treatment with deoxycoformycin (DCF), the MNCs remained essentially constant throughout therapy with no evidence of a co- existing T-cell clone to account for the TCR beta rearrangement. Although MNCs from this patient bound significantly less IFN-alpha than did MNCs from other HCL patients, the binding was of high affinity with a kd similar to that of control cells. The number of IFN-gamma receptors on our patient's MNCs was four times higher than the number of IFN-alpha receptors and was similar to the number of IFN-alpha receptors on MNCs from HCL patients responsive to IFN-alpha. While various treatments including IFN-alpha, DCF, chlorambucil, splenectomy, leukopheresis, and IFN-gamma were not able to change the clinical progression of the disease, they may have provided an opportunity for the divergent TCR beta rearranged clone to expand and displace the initially dominant clone.

Dual rearrangement of immunoglobulin and T-cell receptor gene in a case of T-cell hairy-cell leukemia

2009 ◽  
Vol 46 (2) ◽  
pp. 71-76 ◽  
Author(s):  
Antonio P. Palumbo ◽  
Paolo Corradini ◽  
Silvano Battaglio ◽  
Paola Omedè ◽  
Renato Coda ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Hairy Cell Leukemia ◽  
Receptor Gene ◽  
Cell Receptor ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
T Cell Receptor Gene ◽  
Cell Receptor Gene

scholarly journals Hairy cell leukemia associated with large granular lymphocyte leukemia: immunologic and genomic study, effect of interferon treatment

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 655-660 ◽  
Author(s):  
JP Marolleau ◽  
T Henni ◽  
P Gaulard ◽  
JP Le Couedic ◽  
MF Gourdin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Cell Receptor ◽  
Hairy Cell Leukemia ◽  
Gene Rearrangement ◽  
Cell Receptor ◽  
Large Granular Lymphocyte ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Ifn Treatment

Abstract The authors describe a patient who presented an association of hairy cell leukemia (HCL) and large granular lymphocyte (LGL) leukemia. An eventual relationship between these two rare entities is analyzed. Hairy cells (HCs) were present in the blood, bone marrow, and spleen. An excess of LGLs was found only in the blood and bone marrow. After splenectomy the patient received an alpha 2-interferon (alpha 2-IFN) treatment. The HCs surface phenotype was mu+delta+kappa+, CD20+, and CD25+. The LGLs consisted in CD3+, CD8+, HNK1+, WT31+ T lymphocytes. These were absent in the spleen. alpha 2-IFN treatment resulted in the disappearance of the HCs in the blood and bone marrow, whereas the LGLs remained unchanged. Before alpha 2-IFN treatment, peripheral blood cells, predominantly LGLs, exerted low cytotoxicity that increased up to a normal level after treatment. Using Southern blotting the authors studied the rearrangements of the T-cell receptor beta--chain (C beta) and gamma-chain (J gamma) genes and immunoglobulin heavy (JH)- and light (C kappa, C lambda)- chain genes. An unique JH and C kappa gene rearrangement was found in the blood and spleen, whereas C beta and J gamma gene rearrangements were present in the blood, not in the spleen. Under alpha 2-IFN treatment, the JH gene rearrangement fainted dramatically, in contrast to that of the C beta gene. The study of messenger RNA (mRNA) of the T cell receptor alpha and beta chains evidenced the 1.3-kilobase (kb) and 1.6-kb bands in the blood and their absence in the spleen. The patient was human T-cell leukemia virus (HTLV)-II negative by Southern analysis of blood and spleen cells. It is concluded that the LGL expansion was clonal and not reactive to the HCL. Although the authors cannot definitely exclude that both HC and LGL proliferations stem in a common leukemic precursor, their findings support an association of the two entities.

scholarly journals Hairy cell leukemia associated with large granular lymphocyte leukemia: immunologic and genomic study, effect of interferon treatment

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 655-660
Author(s):  
JP Marolleau ◽  
T Henni ◽  
P Gaulard ◽  
JP Le Couedic ◽  
MF Gourdin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Cell Receptor ◽  
Hairy Cell Leukemia ◽  
Gene Rearrangement ◽  
Cell Receptor ◽  
Large Granular Lymphocyte ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Ifn Treatment

The authors describe a patient who presented an association of hairy cell leukemia (HCL) and large granular lymphocyte (LGL) leukemia. An eventual relationship between these two rare entities is analyzed. Hairy cells (HCs) were present in the blood, bone marrow, and spleen. An excess of LGLs was found only in the blood and bone marrow. After splenectomy the patient received an alpha 2-interferon (alpha 2-IFN) treatment. The HCs surface phenotype was mu+delta+kappa+, CD20+, and CD25+. The LGLs consisted in CD3+, CD8+, HNK1+, WT31+ T lymphocytes. These were absent in the spleen. alpha 2-IFN treatment resulted in the disappearance of the HCs in the blood and bone marrow, whereas the LGLs remained unchanged. Before alpha 2-IFN treatment, peripheral blood cells, predominantly LGLs, exerted low cytotoxicity that increased up to a normal level after treatment. Using Southern blotting the authors studied the rearrangements of the T-cell receptor beta--chain (C beta) and gamma-chain (J gamma) genes and immunoglobulin heavy (JH)- and light (C kappa, C lambda)- chain genes. An unique JH and C kappa gene rearrangement was found in the blood and spleen, whereas C beta and J gamma gene rearrangements were present in the blood, not in the spleen. Under alpha 2-IFN treatment, the JH gene rearrangement fainted dramatically, in contrast to that of the C beta gene. The study of messenger RNA (mRNA) of the T cell receptor alpha and beta chains evidenced the 1.3-kilobase (kb) and 1.6-kb bands in the blood and their absence in the spleen. The patient was human T-cell leukemia virus (HTLV)-II negative by Southern analysis of blood and spleen cells. It is concluded that the LGL expansion was clonal and not reactive to the HCL. Although the authors cannot definitely exclude that both HC and LGL proliferations stem in a common leukemic precursor, their findings support an association of the two entities.

scholarly journals B-ly-7, a monoclonal antibody reactive with hairy cell leukemia, also defines an activation antigen on normal CD8+ T cells [see comments]

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 959-964 ◽  
Author(s):  
SP Mulligan ◽  
P Travade ◽  
E Matutes ◽  
C Dearden ◽  
L Visser ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Hairy Cell Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Activation Antigen

Abstract 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 reactivity 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 reacted with all 28 cases examined, as well as with 3 of 9 cases of a variant form of HCL. Cells of other closely related B-cell disorders, prolymphocytic leukemia, and splenic lymphoma with villous lymphocytes were negative. Investigation of the peripheral blood and bone marrow of patients with HCL before and after treatment with alpha-interferon or deoxycoformycin suggests that B-ly-7 may be useful in the assessment of minimal disease after therapy. In addition to HCL, we found that B-ly-7 was positive with cells of three mature, CD4+ T-cell malignancies. In view of the reactivity with malignancies of activated B and T cells, we searched for the expression of B-ly-7 on activated, normal B and T cells and found that B-ly-7 reacted specifically with activated normal peripheral blood CD8+ T cells. B-ly-7 has a number of applications, including the precise classification of mature B-cell neoplasia and the diagnosis HCL and its assessment after treatment. In addition, B-ly-7 recognizes a small subset of T-cell disorders. Its expression on these malignancies and on in vitro activated peripheral blood CD8+ T cells suggests that B- ly-7 detects a lymphocyte activation antigen.

scholarly journals Response to 2'-deoxycoformycin after failure of interferon-alpha in nonsplenectomized patients with hairy cell leukemia

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 297-300
Author(s):  
KA Foon ◽  
GM Nakano ◽  
CA Koller ◽  
DL Longo ◽  
RG Steis
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Hairy Cell Leukemia ◽  
Subsequent Treatment ◽  
Spleen Size ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Massive Splenomegaly ◽  
Ifn Alpha ◽  
Severe Pancytopenia

Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2′-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients.

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 Integrated human T-cell leukemia virus II genome in CD8 + T cells from a patient with "atypical" hairy cell leukemia: evidence for distinct T and B cell lymphoproliferative disorders

Blood ◽  
1988 ◽  
Vol 71 (2) ◽  
pp. 363-369
Author(s):  
JD Rosenblatt ◽  
JV Giorgi ◽  
DW Golde ◽  
JB Ezra ◽  
A Wu ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Hairy Cell Leukemia ◽  
Mononuclear Cells ◽  
Lymphoproliferative Disorders ◽  
Lymphoid Cells ◽  
T Cell Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Human T Cell

We previously reported isolation of human T-cell leukemia virus II (HTLV-II) from a second patient (N.R.A.) with atypical hairy cell leukemia. Follow-up analysis of the characteristics of the patient's HTLV-II infection over a 2-year period has revealed that the patient had two coexistant lymphoproliferative disorders. Oligoclonally integrated HTLV-II was detected in DNA extracted from the patient's peripheral blood mononuclear cells on separate occasions greater than 1 year apart, similar to integration of HTLV-I seen in adult T cell leukemia/lymphoma. Although integrated provirus was readily detected, no HTLV-II viral RNA expression was seen in fresh peripheral blood lymphoid cells. Although the patient's peripheral blood consistently contained a majority of atypical lymphoid cells with a T cell antigenic phenotype, he ultimately developed extensive pleural, hepatic and soft tissue infiltration with malignant Tac+, tartrate-resistant, acid phosphatase-positive (TRAP+) B cells of clonal origin. To further characterize the role of HTLV-II, the patient's peripheral blood mononuclear cells were fractionated into four enriched subpopulations at autopsy. Oligoclonally integrated HTLV-II was detected in DNA from a T cell-enriched fraction and a CD8+ T cell-enriched fraction, but not in a CD4+ T cell-enriched fraction, a non-T cell fraction, or in B cells obtained from the malignant pleural effusion. We conclude that the patient harbored two distinct lymphoproliferative disorders, a TRAP+, Tac+ B cell malignancy consistent with hairy cell leukemia that did not contain HTLV-II and a Tac-, CD8+ lymphoproliferative syndrome with oligoclonally integrated HTLV-II.

scholarly journals Integrated human T-cell leukemia virus II genome in CD8 + T cells from a patient with "atypical" hairy cell leukemia: evidence for distinct T and B cell lymphoproliferative disorders

Blood ◽  
1988 ◽  
Vol 71 (2) ◽  
pp. 363-369 ◽  
Author(s):  
JD Rosenblatt ◽  
JV Giorgi ◽  
DW Golde ◽  
JB Ezra ◽  
A Wu ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Hairy Cell Leukemia ◽  
Mononuclear Cells ◽  
Lymphoproliferative Disorders ◽  
Lymphoid Cells ◽  
T Cell Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Human T Cell

Abstract We previously reported isolation of human T-cell leukemia virus II (HTLV-II) from a second patient (N.R.A.) with atypical hairy cell leukemia. Follow-up analysis of the characteristics of the patient's HTLV-II infection over a 2-year period has revealed that the patient had two coexistant lymphoproliferative disorders. Oligoclonally integrated HTLV-II was detected in DNA extracted from the patient's peripheral blood mononuclear cells on separate occasions greater than 1 year apart, similar to integration of HTLV-I seen in adult T cell leukemia/lymphoma. Although integrated provirus was readily detected, no HTLV-II viral RNA expression was seen in fresh peripheral blood lymphoid cells. Although the patient's peripheral blood consistently contained a majority of atypical lymphoid cells with a T cell antigenic phenotype, he ultimately developed extensive pleural, hepatic and soft tissue infiltration with malignant Tac+, tartrate-resistant, acid phosphatase-positive (TRAP+) B cells of clonal origin. To further characterize the role of HTLV-II, the patient's peripheral blood mononuclear cells were fractionated into four enriched subpopulations at autopsy. Oligoclonally integrated HTLV-II was detected in DNA from a T cell-enriched fraction and a CD8+ T cell-enriched fraction, but not in a CD4+ T cell-enriched fraction, a non-T cell fraction, or in B cells obtained from the malignant pleural effusion. We conclude that the patient harbored two distinct lymphoproliferative disorders, a TRAP+, Tac+ B cell malignancy consistent with hairy cell leukemia that did not contain HTLV-II and a Tac-, CD8+ lymphoproliferative syndrome with oligoclonally integrated HTLV-II.

scholarly journals Response to 2'-deoxycoformycin after failure of interferon-alpha in nonsplenectomized patients with hairy cell leukemia

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 297-300 ◽  
Author(s):  
KA Foon ◽  
GM Nakano ◽  
CA Koller ◽  
DL Longo ◽  
RG Steis
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Hairy Cell Leukemia ◽  
Subsequent Treatment ◽  
Spleen Size ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Massive Splenomegaly ◽  
Ifn Alpha ◽  
Severe Pancytopenia

Abstract Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2′-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients.

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