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H Merle-Béral

Publications and source records attributed to H Merle-Béral.

50 records · Page 3Linked to original sources

Interleukin 4 counteracts the interleukin 2-induced proliferation of monoclonal B cells.

B cells from patients suffering from B-type chronic lymphocytic leukemia (B-CLL) are susceptible to the effects of several interleukins. Using the cells from 12 different patients we show that IL-4 does not synergize with anti-mu antibody for the enhancement of DNA synthesis. Moreover IL-4 profoundly (90%) suppresses the response to IL-2 in the 10 patient responders to this interleukin. This suppression occurs whether IL-2 is used alone, in costimulation with anti-mu antibody, or in synergy with IFN-gamma. In no instance did IL-4 induce terminal differentiation. This negative effect of IL-4 can take place in monoclonal B-CLL cells where IL-4 enhances the expression of CD23. IL-4 does not interfere with the upregulation of CD25 by IL-2. Thus, IL-4 may display inhibitory effects on the proliferative response of selected B cell populations. The antagonism between IL-4 and IL-2 has important implications for the potential use of cytokines in the management of B-CLL patients.

Antibodies↗

Induction of differentiation in human leukemic B cells by interleukin 2 alone: differential effect on the expression of mu and J chain genes.

The effects of interleukin 2 (IL2) on the proliferation and differentiation of B cells were analyzed separately using cells from two patients suffering from B-type chronic lymphocytic leukemia. The monoclonal B cells from these patients exhibited an opposite pattern of responsiveness upon in vitro culture with IL2 in the absence of other stimuli. In the first patient, IL2 alone was able to induce DNA synthesis and no Ig production. In the second patient, although no DNA synthesis was detected, B lymphocytes synthesized IgM upon stimulation with IL2 alone. Analysis of mRNA levels was performed on the cells of this latter patient after culture without or with IL2. In the presence of IL2 we observed a strong enhancement of C mu gene expression associated with an increase of the ratio between the secreted form and the membrane-bound form of mu mRNA. In contrast IL2 induced only a marginal enhancement of J chain mRNA. Thus, terminal B cell differentiation of selected monoclonal B cells can be obtained in the absence of DNA synthesis and IL2 alone can mediate this process. Moreover, IL2 can act at selective steps of the molecular events associated with IgM production. These results document the multiple effects of a given IL on the events leading to antibody production and strongly suggest that they can be conditioned by the maturation stage of a given responding cell.

B-Lymphocytes↗

CD1 expression in B-CLL cells.

The peripheral blood from 38 B-CLL patients was studied by flow cytometry with 25 clustered or not clustered monoclonal antibodies (moAbs) in order to characterize the cell surface phenotype of lymphoid cells. All moAbs were chosen since they detected B or CD1-8 T cell differentiation antigens or MHC class II antigens. The results showed a heterogeneity in the leukemic cell reactivity with the various moAbs and between patients. The restricted B cell antigens recognized by BL14, Y2955 and anti-class II moAbs were constantly expressed in leukemic cells, while B-cell antigens reacting with FMC7 and BL13 moAbs were variably detected. In addition to CD5 antigens, other T cell markers including several epitopes of the CD1 group were also found to be present on the leukemic cell surface in several cases. To further extend these data, 6 cases were selected for labelling with a battery of 6 CD1a, 2 CD1b and 1 CD1c moAbs. These results suggested that CD1a,c epitopes can be detected on leukemic B cells in addition to other T cell differentiation antigens.

Antibodies, Monoclonal↗

Functional heterogeneity of B-CLL lymphocytes: dissociated responsiveness to growth factors and distinct requirements for a first activation signal.

We studied the effects of B cell directed growth factors on B lymphocytes from 11 patients with chronic lymphocytic leukemia (B-CLL). B-CLL lymphocytes were costimulated with anti-mu antibody (Ab) and with three growth factor preparations: recombinant IL2, B cell growth factor (BCGF) (20 kiloDalton (kD) BCGF) and a high molecular weight BCGF (50 kD BCGF). IL2 was the more active factor (in six of 11 patients). The effect of IL2 was dependent on a costimulation with anti-mu Ab or occurred independently of anti-mu Ab, according to the patients. This pattern of reactivity did not correlate with the presence or absence of the IL2 receptor (IL2-R) molecule on fresh B-CLL lymphocytes. Five patients responded to the 20 kD BCGF. Although four of them were also strong responders to IL2, one strongly responded to the 20 kD BCGF and did not respond to IL2. Only one patient responded to the 50 kD BCGF. When an anti-IL2-R Ab was introduced into the culture, only the responsiveness to IL2 was abolished: thus both 20 kD and 50 kD BCGFs activate B-CLL lymphocytes independently of the IL2-R. These results show that several B cell directed growth factors can act independently to support the proliferation of B-CLL lymphocytes.

Antigens, Surface↗

[Myeloid differentiation antigens: characterization and expression in acute myeloblastic leukemias].

We report the main characteristics of myeloid clusters of differentiation, recently described and confirmed at the 3rd International Workshop on Human Leukocyte Differentiation Antigens (Oxford, September 1986). The principal studies concerning immunopheno-typing of acute myeloblastic leukemias, its concordance with the FAB classification, and its prognostic implications are analysed.

Antigens, Differentiation↗

[Biological aspects of chronic lymphoid leukemia].

The present study is concerned with clinical prognostic classifications of chronic lymphocytic leukemia derived from numerous statistics and multivariate survival analysis. We analyse the prognostic significance of some biological patterns: bone marrow histological studies, lymph node biopsies, size, structure and doubling time of blood lymphocytes, tumoral markers and karyotype analysis. The problem of the monoclonal clone origin is discussed: differentiation abnormality or proliferation of a physiological clone.

Female↗

Extended versus involved fields irradiation combined with MOPP chemotherapy in early clinical stages of Hodgkin's disease.

From 1976 to 1981, 335 patients with untreated Hodgkin's disease, clinical stages I, II, and IIIA, have been treated by MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy, three to six cycles according to the prognostic factors, combined with radiotherapy. Irradiation was always performed after the first three cycles of chemotherapy, and was randomized between extensive radiotherapy, ie, mantle and paraaortic areas for supradiaphragmatic presentations, and radiotherapy restricted to the involved areas. No significant difference was observed between the two randomized branches for the disease-free survival (86% after six years in the involved field branch v 90% in the extended field branch), and none for the overall survival. Most of the relapses occurred in nonirradiated areas in the first group, and in irradiated areas in the second. Relapses were especially frequent in the IIE stages with pulmonary extension; extranodal relapses occurred with osseous and cutaneous localizations. Two cases of secondary leukemia were observed after three- or six-cycle MOPP plus radiotherapy limited to the involved areas.

Adolescent↗

[Evaluation of the performance of Spectrum III].

For 8 months we have studied the performance of the laser flow cytometry system Spectrum III (Ortho Diagnostic Systems). We have investigated problems caused by the setting and the calibration, assessment of the rhythm, the repetitiveness and the contamination, and compared the results obtained with the Spectrum III with those obtained using a fluorescence microscope. As an example of an immunopathological application, we have assessed the results obtained in the analysis of peripheral blood from 20 patients with B cell chronic lymphocytic leukemia and 300 suspect AIDS patients.

Acquired Immunodeficiency Syndrome↗

[Evaluation of the performance of Coulter S+II].

The technical performances of the Coulter S+II counter was evaluated for lymphocyte counts and the data obtained were compared to those supplied by the ELT 800 analyzer to the results for manual and Hemalog D counting methods. We assessed accuracy of three types of information supplied by the S+II model in the following conditions: erythrocyte indices in anemia, white cell histograms in chronic myeloid leukemia, chronic lymphoid leukemia, acute leukemia and eosinophilia, and the reliability of the analyzer in showing the degree of thrombopenia and hyperthrombocytosis.

Anemia↗

AIDS-related primary lymphoma of the pleural cavity. A case report.

BACKGROUND: Pleural effusions are common in patients with the acquired immunodeficiency syndrome (AIDS). Their most frequent causes are Kaposi's sarcoma and mycobacterial infections. We report cytologic, immunophenotypic and molecular features of a primary pleural non-Hodgkin's lymphoma (NHL) that represent an uncommon cause of isolated pleural effusion in patients with AIDS. CASE: A 66-year-old, human immunodeficiency virus-positive male presented with chest pain and dyspnea. He had no history of opportunistic infections or Kaposi's sarcoma. A chest radiography displayed a right-sided pleural effusion. Cytology of pleural fluid revealed lymphomatous cells with markedly irregular nuclei. Their immunophenotype was indeterminate. Computed tomography of the thorax and abdomen did not show any tumor mass. Molecular analysis demonstrated that the lymphomatous cells had a B-cell genotype and contained Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) DNA sequences. CONCLUSION: This case belongs to a new subgroup of AIDS-related NHL that is characterized by unusual morphology, null immunophenotype, B-cell genotype and association with both KSHV and EBV.

Aged↗

Chromosomal DNA and p53 stability, ubiquitin system and apoptosis in B-CLL lymphocytes.

The ubiquitin system regulates diverse biological processes such as DNA replication and repair, biogenesis of ribosome, peroxisome and nucleosome, cell cycle, stress response and signal transduction pathways. Thus, the reported role of the ubiquitin system in apoptotic death control as well the alteration of its control in carcinogenesis should come as no surprise. Indeed, we and other groups have reported that the ubiquitin system is involved in apoptotic cell death of normal human lymphocytes and that this control is altered in B lymphocytes derived from chronic lymphocytic leukemia patients (B-CLL), rendering these malignant cells hypersensitive to specific inhibition of protein degradation/processing through proteasomal function. This approach recently allowed us to demonstrate that the stability of the tumor suppressor and pro-apoptotic protein p53 is differentially regulated in B-CLL versus normal lymphocytes and that this difference might at least partly explain the impaired response of B-CLL lymphocytes to apoptotic death activation. These results strongly suggest an imbalance in p53 regulation in B-CLL cells that leads to a variable response to DNA damage and constitutively expressed chromosomal instability. The question we and others would like to address is whether this alteration, or more likely a subset of alterations of the ubiquitin-proteasome pathway, is specific to B-CLL malignancy or if it is a hallmark of cancer cells in general. In either case, a better understanding of the ubiquitin-dependent control of apoptosis should pave the way towards a methodological approach for in vitro development of discriminating treatments which may be of potential usefulness in clinical trials of B-CLL.

Apoptosis↗

Expression of CD23 by human bone marrow stromal cells.

CD23 is a surface antigen expressed by a variety of human hematopoietic cells and shown to display multiple biological functions. In present work, we assayed CD23 expression by human bone marrow (BM) or by stromal cells derived from this tissue. While freshly isolated BM-cells showed low CD23 expression, a subset of long term BM-culture (LTBMC)-derived stromal cells expressed CD23 mRNA at high levels in their steady state and secreted soluble CD23 in their culture supernatants. To assay the role of CD23 in LTBMC, these cultures were initiated in the presence of neutralizing anti-CD23 mAb. A dramatic decrease in total numbers of hematopoietic cells and CFU-GM recovery was observed in these cultures as compared to controls. These data suggest a role of CD23 expression in stroma cell functions and further confirm the ability of this antigen to regulate human hematopoietic cell development.

Antibodies, Monoclonal↗