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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the direct effects of interferon (IFN) on hairy cells (HCs) isolated from patients with hairy cell leukemia using one- and two-dimensional gel electrophoresis. We have previously characterized the induction of synthesis of 10-16 specific proteins by IFN-alpha 2b in HCs, as analyzed by one-dimensional electrophoresis. By two-dimensional electrophoresis, we have now confirmed this induction and shown that the synthesis of the same number of specific proteins is down-regulated in HCs exposed to IFN-alpha 2b. When compared to HCs, fewer proteins are induced by IFN-alpha 2b in other normal, or neoplastic, lymphoid cells. We also report that protein induction occurs in HCs exposed in vivo to IFN-alpha 2b. We have demonstrated the presence of tubuloreticular structures in the cytoplasm of HCs exposed to IFN-alpha 2b in vitro, using transmission electron microscopy. We now report that these too are seen in HCs exposed to IFN in vivo during therapy. We investigated the effects of IFN-gamma on HCs and found that it also induces specific proteins. The pattern of induced proteins is distinctly different after IFN-gamma exposure in vitro. The fact that such induction occurs suggests that HCs possess also a receptor for IFN-gamma. These results demonstrate that there are direct effects of IFN-alpha on HCs and that such direct effects might be important in the antitumor activity of IFN-alpha in hairy cell leukemia.
Leukemia 1987 Apr
PMID:Action of interferons in hairy cell leukemia. 244 30

Hairy cell leukemia (HCL) is a pre-plasma B cell tumor which responds to interferon (IFN)-alpha therapy. In vitro, B cell growth factor (BCGF) can induce proliferation of hairy cells. We have investigated the effect of in vitro and in vivo treatments with different recombinant IFN on the capacity of hairy cells to proliferate in response to human BCGF. In vitro treatment of leukemic cells from HCL patients with recombinant IFN-alpha-2 (5/5 cases) or IFN-beta (4/5 cases) resulted in a marked inhibition of the BCGF-dependent response. This suppressive effect was obtained with IFN concentrations of 1000, 100 IU/ml, and even occasionally 10 IU/ml. In contrast, no such inhibition was observed with IFN-gamma, despite the presence of specific IFN-gamma receptors on hairy cells at densities similar to receptors for IFN-alpha/beta. The IFN-alpha-induced suppression of the proliferative response of hairy cells to BCGF was also observed in vivo in two patients within 6-12 hr after administration of single doses of IFN-alpha. When hairy cells were maintained in culture for 1 week, they recovered their capacity to be stimulated by BCGF. This reversion was also shown in vivo in hairy cells isolated 1 week after IFN administration. Since in vivo growth of hairy cells could possibly result from the autocrine secretion of BCGF, we propose that the therapeutic effect of IFN-alpha on HCL may be due in part to an inhibition of such autocrine loop.
Leukemia 1987 Aug
PMID:Proliferative response of hairy cells to B cell growth factor (BCGF): in vivo inhibition by interferon-alpha and in vitro effects of interferon-alpha, -beta, and -gamma. 244 36

We investigated the clinical value of immunotyping in 145 consecutive adult patients with absolute or relative lymphocytosis: 132 (91%) had B-cell lymphocytosis, 5 (4%) had T-cell lymphocytosis, 2 (1%) had hairy cell leukemia, and 6 (4%) had reactive lymphocytosis. Of the five patients with T-cell lymphocytosis, four were best categorized as having T gamma-chronic lymphoproliferative disease and had an indolent clinical course. Of the 132 patients with B-cell lymphocytosis, 121 (92%) had B-cell chronic lymphocytic leukemia (B-CLL), and 11 (8%) had small cleaved ("lymphosarcoma") cell leukemia. Patients with small cleaved cell leukemia had a worse clinical outcome than did those with B-CLL. We further analyzed the surface immunoglobulin (sIg) and CD20 (B-1) antigen expression patterns in B-CLL to determine whether any correlation existed with clinical outcome. A subset of patients with B-CLL in whom sIg was expressed in less than 20% of their lymphocytes had the best clinical outcome. HLA-DR (Ia-like) antigen typing helped identify B-CLL cases with minimal or no sIg expression. CD20 (B-1) antigen was weak or undetectable in most cases of B-CLL. Patients with B-CLL who had CD20 (B-1) in more than 20% of their lymphocytes did not have a different prognosis. Our data provide the incidence and natural history of the various subsets of CLL in a series of patients at a single institution. The type and extent of immunotyping necessary and practical in the clinical management of patients with CLL are explored.
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PMID:Role of immunotyping in chronic lymphocytosis: review of the natural history of the condition in 145 adult patients. 245 33

The concomitant presence of B antigens and of the antigen recognized by the monoclonal antibody Leu-M5 (CD11c) on neoplastic lymphoid cells has been reported to be largely restricted to hairy cell leukemia (HCL). The authors studied Leu-M5 reactivity of neoplastic cells from 59 patients whose specimens were referred with a stated diagnosis of HCL by using the alkaline phosphatase anti-alkaline phosphatase technique on peripheral blood (PB) and bone marrow (BM) specimens. Tartrate-resistant acid phosphatase (AcP-T) activity was also studied. In 49 patients, HCL had been confirmed previously by BM biopsy, and specimens were evaluated for disease status during or after therapy with interferon (IFN) or 2'-deoxycoformycin. The remaining ten patients were newly referred for confirmation of the diagnosis of HCL before therapy. In all 55 patients in whom the BM biopsy demonstrated HCL, virtually every leukemic cell was Leu-M5 reactive, and the reaction proved, in some cases, to be helpful in the detection of small numbers of hairy cells in PB or BM preparations. AcP-T reactivity was demonstrated in the neoplastic cells of 52 of these 55 patients, including all but 3 of those receiving IFN, and was helpful in confirming persistent leukemia when interpretation of BM biopsy sections was difficult because the numbers of hairy cells were small. However, in four of the ten newly referred patients, BM biopsy showed features of splenic lymphoma with villous lymphocytes, rather than HCL. The neoplastic cells of these four patients were of B-cell origin and in three were Leu-M5 reactive. The authors' study indicates that Leu-M5 is present in nearly all hairy cells, but its presence in conjunction with other B-cell markers is not specific for HCL.
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PMID:Evaluation of Leu-M5 (CD11c) in hairy cell leukemia by the alkaline phosphatase anti-alkaline phosphatase technique. 245 31

An increased number of serine esterase non-B lymphocytes including CD4+ helper/cytotoxic cells were observed in hairy-cell leukemia patients during (56 +/- 18) and immediately post (52 +/- 16) alpha-interferon therapy compared with pretreatment status (17 +/- 5) and normal donors (29 +/- 3). This increase in lymphocytes bearing one of the putative cytotoxicity-linked proteins was paralleled by a higher cytotoxicity towards K562 cells in the NK and LDCC assays during therapy and similarly, but to a much reduced level, against the hairy-cell derived JOK-1 target cells. Phenotypically, a higher percentage of non-B cells also expressing DR or CD11 antigens were seen in the HCL patients during IFN therapy. In lymphocyte target binding assays, a high affinity of effector to target conjugate formation was observed when either of the hairy cell lines JOK-1 or Hair-M was chosen as targets for IFN-therapy effector cells. Although predominantly CD4+ cells exhibited the in vitro affinity for effector/target conjugation with autologous HCs, the polarisation of serine esterase activity towards the E/T membrane contact area was shown by both CD4+ and CD8+ cells during a short incubation period and before target cell death.
Leukemia 1989 May
PMID:Demonstration of the increase in serine esterase-positive T cells in hairy-cell leukemia patients undergoing alpha-interferon therapy. 249 82

A soluble form of CD8 antigen (sCD8) has been shown to be released by activated CD8 + lymphocytes. Measurements of sCD8 may serve as an index of suppressor/cytotoxic cell activity. To assess the clinical significance of this observation in response to malignancy, we have investigated the sCD8 concentrations in 38 patients with hairy cell leukemia (HCL) not yet treated with any systemic therapy. The median plasma sCD8 level of the 20 nonsplenectomized patients was 1,025 U/ml and was significantly higher than that in the 18 patients who had previous splenectomy (median = 200 U/ml, p less than 0.0001), or in 14 normal controls (median = 350 U/ml, p less than 0.0001). Compared to controls, splenectomized patients had also significantly lower levels of sCD8 (p less than 0.01). The median concentration of soluble interleukin-2 receptor (sIL2R) in nonsplenectomized patients was 14,500 U/ml and was in the same range as in splenectomized patients (15,000 U/ml). There was no overlap in sIL2-R levels between controls (median = 300 U/ml) and patients. Investigation of serial plasma samples in 7 patients who received deoxycoformycin (DCF) and 11 patients treated with interferon alpha (IFN-alpha) showed a normalization of sCD8 levels and a decrease of sIL2R concentrations in those patients who showed hematological improvement. Normalization of sIL2R was, however, only observed in patients with complete remission. Our observation indicates that splenectomy might cause a reduction of the activation of suppressor/cytotoxic cells in patients with HCL. Treatment with either DCF or IFN-alpha also modulates the sCD8 levels to normal range. Measurements of sCD8 and sIL2-R might give more insight into the pathogenesis of HCL and serve as parameters for monitoring different phases of the disease and response to therapy.
Leukemia 1989 Oct
PMID:Plasma levels of soluble CD8 antigen and interleukin-2 receptor antigen in patients with hairy cell leukemia, relationship with splenectomy and with clinical response to therapy. 250 98

We reported a case of chronic B-cell leukemia reacted to the administration of 1 alpha (OH)D3 (Alfarol-CHUGAI Pharm. Co.), The patient showed pancytopenia with IgM-kappa type monoclonal protein in the serum. The bone marrow aspiration was failed due to a dry tap, but the biopsied specimen showed a marked infiltration of small sized lymphoid cells with wide cytoplasm. The leukemic cells from peripheral blood showed a morphology of atypical hairy cells, Surface markers of the leukemic cells were IgM, D(kappa)+, CD 19+, CD 20+, CD 21- and HLADR+, The leukemic cells showed no L-tartrate resistant acid phosphatase sensitivity. This case was diagnosed as a chronic B-cell leukemia closely related to a hairy cell leukemia. The treatment with estrogen-chlorambucil compound (Bestrabucil-KUREHA Chem, Co.) or splenic irradiation was not effective. However, after two months' administration of Alfarol the regular blood transfusion was not needed because of increment of the Hb concentration. After eight months of its administration, the bone marrow aspirate showed a marked decrease in the number of the leukemic cells and a restoration of normal hematopoietic cells. This experience suggested that Alfarol in usefull for the treatment of chronic B cell leukemia including hairy cell leukemia and chronic lymphocytic leukemia.
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PMID:[1 alpha(OH) D3 (Alfarol) is effective for the treatment of chronic B cell leukemia: a case report]. 259 55

The Italian Cooperative Group for Hairy Cell Leukaemia (ICGHCL), between April 1985 and June 1987, conducted a multicentre study using human lymphoblastoid alpha-interferon as primary therapy as an alternative to splenectomy. Forty-eight evaluable patients with HCL entered the study, 38 of them had splenomegaly, in five patients the spleen was not palpable and five were unfit for surgery because of age and general condition. Daily dose of 3 MU s.c. alpha-IFN was given for 12 weeks, or until a satisfactory and stable response was obtained. Among these 48 patients the response rate after 3 months of therapy was 63%, with seven patients (15%) achieving complete remission and 23 (48%) partial remission; 13 (27%) patients had a minor response. In five patients no response was observed and they died within 2 months of treatment. Five other patients, after an initial response, presented a re-expansion of the disease. Actuarial survival at 30 months was 88.8% for the entire group of 48 patients and 92% for the 38 patients who would normally be treated by splenectomy. Thus, alpha-IFN as primary treatment in HCL offered a reasonable therapy for splenomegalic patients. The timing and validity of splenectomy still remains an open question.
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PMID:Human lymphoblastoid interferon as initial therapy in hairy cell leukaemia: a multicentre study in non-splenectomized patients. Italian Cooperative Group for Hairy Cell Leukemia. 266 Sep 1

The authors conducted a histopathologic study on tissues from 11 patients with the recently described syndrome of large granular lymphocyte (LGL) leukemia. Distinctive pathologic findings were found most often in the bone marrow, liver, and spleen. The bone marrow biopsies contained nonparatrabecular lymphoid infiltrates that were nodular or diffuse and interstitial. Plasmacytosis was found and in two cases there was myeloid maturation arrest. The liver biopsies contained sinusoidal and portal infiltrates and the spleen had red pulp cord and sinus infiltrates, plasmacytosis, and follicular hyperplasia. Lymph node involvement was nondiagnostic, consistent with the usual absence of lymphadenopathy. The morphologic findings were sometimes indistinguishable from other reactive or low-grade lymphoproliferative disorders, especially chronic lymphocytic leukemia/well-differentiated lymphocytic lymphoma (CLL/WDLL) and hairy cell leukemia. These results suggest the need to correlate peripheral blood cell counts and morphology as well as immunophenotypic studies with tissue histology to distinguish LGL leukemia from other disorders. Establishing a correct diagnosis of LGL leukemia may help clarify the etiology of unexplained peripheral blood cytopenias, arthritis, and other autoimmune manifestations in individual patients.
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PMID:The pathology of large granular lymphocyte leukemia. 231 87

Hairy cell leukemia is a distinct chronic lymphoproliferative disorder composed of morphologically unique B-lymphocytes. The diagnosis of hairy cell leukemia is usually based on the morphology of blood/bone marrow aspirate smears and bone marrow sections. We report three cases of hairy cell leukemia that had an unusual multilobated nuclear appearance seen on both smears and tissue sections. Many of the hairy cells exhibited marked nuclear lobulations and convolutions, giving rise to clover leaf-like nuclear configurations. The nuclear chromatin was finely reticular and characteristic of hairy cell leukemia. Bone marrow sections were hypercellular and the leukemic infiltrate was loosely distributed. A leukemic infiltrate was also seen in splenic sections in two cases in which splenectomy was carried out. Tartrate-resistant acid phosphatase cytochemistry was positive in all three cases. Flow cytometric analysis and paraffin section immunoperoxidase studies confirmed the B-cell lineage of the leukemic cells in all cases. The multilobulated nuclei described in these three cases are quite unusual in hairy cell leukemia; they could potentially lead to an erroneous diagnosis of T-cell lymphoma or leukemia. Features typical of hairy cell leukemia, such as the nuclear chromatin distribution and pattern of bone marrow infiltration, together with the clinical history, are helpful in establishing a correct diagnosis of these variant cases of hairy cell leukemia.
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PMID:A multilobular variant of hairy cell leukemia with morphologic similarities to T-cell lymphoma. 266 35


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