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H Merle-Béral

Publications and source records attributed to H Merle-Béral.

At least 37 records · Page 2Linked to original sources
PubMed1995

Skewed rearrangement of the VH4-21 gene during pre-B acute lymphoblastic leukemia.

Thirty-six pre-B acute lymphoblastic leukemias (ALL) were studied for VH family expression. Among the 35 detected rearrangements, VH1 family genes were expressed in 7, VH2 in 1, VH3 in 18, VH4 in 6 and VH6 in 3. This expression is close to that expected according to the complexity of the system. The complete sequence of the 6 VH4 genes was examined in order to determine whether there is a skewed rearrangement of individual genes in this family. Our results indicate rearrangement of VH4-21 in 3 cases, 71-4 in one, 58P2 in one case and probably of a new germinal VH4 gene for the sixth case. All the genes were displaying an almost complete homology with their germinal VH counterparts. The 6 sequenced genes associated with 6 different D gene segments displaying a close homology with their germinal counterpart. JH4 segment was expressed in 3 cases and JH6 in the remaining 3. These results associated with previous results obtained by others indicate that there is skewed rearrangement of the VH4-21 gene in pre-B ALL. It is presently unknown whether this phenomenon is the consequence of a selective process or whether it reflects what normally occurs in the normal human functional repertoire, which could be more limited than the germline repertoire.

Adult↗
PubMed1995

[In vitro induction of apoptosis in chronic lymphoid leukemia B lymphocytes by theophylline: therapeutic applications].

In a case of indolent stage A chronic lymphocytic leukemia (C.L.L.), treated for ten years only by theophylline for bronchial asthma, we observed spontaneous apoptosis of B lymphocytes (10%). As suggested by these case report, we described new properties of methylxanthine derivatives. In vitro, theophylline increased spontaneous apoptosis after 72 hours in culture of 6 patients by a mean percentage of 80-90% in B-C.L.L. blood lymphocytes (control 20%). Dose-dependent apoptosis involves cyclic nucleotides (AMPc). Using identical theophylline doses, we did not observe apoptosis of normal peripheral blood B lymphocytes. According to French ethical rules, we treated 8 patients with the same doses of theophylline than for bronchial asthma without responses. On the other hand, in 12 aggressive forms of C.L.L., resistant or in relapsed after alkylating agents, methylxanthine derivatives appeared a powerful adjuvant of chlorambucil treatment. We observed 11 responses with less dose of alkylating agents than in previous treatment: decrease in the concentration of blood lymphocytes (11 patients) and clinical remissions (8 patients). Mechanism of action and future of this new drugs combination in the treatment of C.L.L. are discussed.

Aged↗
PubMed1994

Maturation of acute T-lymphoblastic leukemia cells after CD2 ligation and subsequent treatment with interleukin-2.

In this study, we have investigated the ability of various cytokines to induce the maturation of acute lymphoblastic leukemia (T-ALL) cells with early T-cell phenotype. Leukemic blasts from 17 untreated T-ALL patients were assayed for their ability to acquire mature T-cell markers, CD3/T-cell receptor (TCR) in particular, after incubation with one or a combination of recombinant human interleukin-1 (IL-1), IL-2, IL-4, IL-7, and CD2-specific monoclonal antibody (MoAb). IL-7 or IL-2 induced the proliferation of some leukemic cells, whereas sequential cell treatment with CD2-MoAb and then IL-2 promoted CD3/TCR expression on nearly all CD2+ cells (15 of 16), except for 1 T-ALL that developed into CD3-CD16+CD56+ cells. Differentiation of T-ALL cells was also evidenced through the downregulation of CD34 precursor cell antigen, the generation of CD4+ and CD8+ cells from CD4+ CD8+ precursors, and the acquisition of mature T-cell functions. CD2 ligation induced a progressive increase of surface expression of IL-2 receptor alpha (IL-2R alpha) and IL-2R beta and an accelerated in vitro death of leukemic cells. The ligation of IL-2R by IL-2 rescued T-ALL cells from death and promoted their progression toward more mature cells expressing extracellular CD3/TCR alpha beta complexes. Intracellular analysis indicates that TCR alpha transcription and membrane translocation of both TCR alpha and TCR beta were promoted in these conditions. Analysis of intracellular signals transduced during T-ALL differentiation indicated that CD2-ligation induced Ca2+ influx and that the ligation of CD2 and IL-2R induced distinct tyrosine phosphorylation patterns. The addition of inhibitors of tyrosine phosphorylation abolished T-ALL cell differentiation, which suggests the involvement of tyrosine kinases in this phenomenon. Together, we showed the constant maturation of leukemic early T cells after stimulation of surface CD2 and the high-affinity IL-2R.

Antibodies, Monoclonal↗
PubMed1994

[Cell Dyn 3000: technical performance and applications in hematologic pathology].

The Abbott Cell-Dyn (CD) 3000 is an automatic analyser, designed to give cell blood counts (CBC) and white blood differential (WBCD) by 4 angels diffraction analysis. Evaluation was performed by comparison between results obtained by CD and those obtained by Technicon H1 and by microscopic examination. Technical performances as reproducibility, linearity, carryover were quite well acceptable. On normal samples, neutrophils (NE), lymphocytes (LY) and eosinophils (EO) were found to correlate with optical method with coefficient (R) values higher than 0.9. Weaker R coefficients were found for monocytes (MO) and basophils (BA), however it didn't involve clinical consequences. Significant threshold for immature granulocytes (IG) and variant lymphocytes (VL) flags were built. By using those, a false positive rate of 7% was shown. In hematological diseases, no false negative was detected because all samples were flagged. However, no acute lymphoblastic leukemia (ALL) was studied, so the detection of lymphoblast, as known as a real difficulty for analyser, was not yet evaluated. Blasts in acute myeloblastic leukemia (AML) and hairy cells were both noticed by CD. Moreover, for chronic lymphocytic leukemia (CLL), three groups were described, according to the flags released. Knowing its performances and its limits, CD is a good analyser usable in an all round or a hematological laboratory with high number of WBCD per day.

Autoanalysis↗
PubMed1994

Performance evaluation of the haematological analyser Cell-Dyn 3000 (Abbott).

The Abbott Cell Dyn (CD) 3000 is an automatic analyser, designed to give a complete blood count (CBC) and white blood cell differential (WBCD) by 4 angle diffraction analysis. This instrument was evaluated by comparison of results obtained with those obtained from a Technicon H1 analyser and by microscopic examination. Technical performances with regard to reproducibility, linearity and carryover was acceptable and in normal samples there was close correlation with the optical method (R > 0.9) for neutrophils (NE), lymphocytes (LY) and eosinophils (EO). Correlation for monocytes (MO) and basophils (BA) was poorer but without clinical consequences. Significant thresholds for immature granulocyte (IG) and variant lymphocyte (VL) flags were determined and using these thresholds the false positive rate was reduced to 7%. In haematological diseases, no false negatives were observed as all samples were flagged. However, since no case of acute lymphoblastic leukaemia (ALL) was studied, the detection of lymphoblasts which is known to present difficulties for analysers remains to be evaluated. Blasts in acute myeloblastic leukaemia (AML) and hairy cells were recognised, while in chronic lymphocytic leukaemia (CLL) it was possible to define 3 groups according to the flags released. The CD appears to be a satisfactory analyser for use in general or haematological laboratories performing a large number of WBCD per day.

Adult↗
PubMed1993

IL-4 release by human leukemic and activated normal basophils.

Recently, authors have addressed the ability of human basophils to produce IL-4. We report here the detection of significant serum IL-4 levels in a case of acute transformation of chronic myelogenous leukemia with a predominant basophilic cell population. Leukemic basophils were isolated from patients' PBMC and assayed for their IL-4-mRNA expression and their ability to secrete this cytokine in vitro. Leukemic basophilic cells (> 90% toluidine blue positive) but not other PBMC expressed IL-4-mRNA, contained IL-4 protein, and secreted this cytokine. These cells had a spontaneous IL-4 secretion ability, without a need for an exogenous activator. Meanwhile, IL-4 release was significantly increased following leukemic cell activation through Fc epsilon RI-ligation or by Ca2+ ionophore. IL-4 and its mRNA were also detected in leukemic basophils from three other chronic myelogenous leukemia patients with moderate basophilia (13, 14, and 23% basophils in PBMC). To confirm these data in normal human cells, we have developed a method to obtain large numbers of purified basophils from human bone marrow cell cultures. In contrast to leukemic basophils, normal cells required in vitro activation through Fc epsilon RI ligation or by Ca2+ ionophore to express and secrete IL-4. Leukemic and normal basophils secreted histamine following in vitro activation, but were negative for tryptase. These data thus demonstrate the in vivo and in vitro ability of human basophils to produce IL-4.

Basophils↗
PubMed1993

Defective calcium response in B-chronic lymphocytic leukemia cells. Alteration of early protein tyrosine phosphorylation and of the mechanism responsible for cell calcium influx.

To study defective signal transduction via the Ag receptor of B-chronic lymphocytic leukemia cells (B-CLL), we examine in this report the Ca2+ response triggered by anti-mu antibody in 23 patients previously classified in three phenotypic groups. Altered Ca2+ changes are essentially found in CLL group II whose leukemic cells are characterized by a marked expression of the CD11b Ag. B-CLL cells from patients with a defective Ca2+ response present an altered pattern of protein tyrosine phosphorylation after anti-mu stimulation in comparison with normal human B cells and B-CLL cells from patients having a normal Ca2+ response. Most of the proteins usually tyrosine phosphorylated after the triggering of cell-surface IgM are concerned. This includes the gamma 1 isoform of phospholipase C, although the protein is normally present in B-CLL cells. These findings suggest that the interruption of the phosphoinositide pathway in B-CLL cells is very proximal, at the level in the signaling cascade between activated surface Ig receptors and protein tyrosine kinases. Simultaneously, we demonstrate that some low responding patients exhibit a decreased Ca2+ response to thapsigargin, an agent known to release intracellular Ca2+ without inositol 1,4,5-trisphosphate production. This suggests that an altered functioning of the mechanism leading to the cell Ca2+ influx in B cells can be also involved in the decreased Ca2+ response observed in B-CLL cells.

Animals↗
PubMed1993

Maturation of human myelomonocytic leukemia cells following ligation of the low affinity receptor for IgE (Fc epsilon RII/CD23).

The regulation of the low affinity receptor for IgE (Fc epsilon RII/CD23) expression and its role were investigated in U937 cell line and in leukemic cells from a patient (Amb) with acute myeloblastic leukemia. Both cell populations were CD23- but could acquire CD23 expression following treatment with IL-4. CD23+ cells, however, remained blastic and did not show any significant phenotypical and functional modifications. Following ligation of the CD23 on U937 and Amb cells by anti-CD23 mAb, these leukemic cells differentiated into mature monocyte/macrophage-like cells. CD23 ligation promoted the expression of the monocyte marker, CD14, increased the expression of the common beta chain of the LFA-1 family (CD18), and down-regulated the expression of the promonocytic marker CD33. Morphological and phenotypical changes were associated with functional modifications as CD23 ligation allowed the acquisition of the oxidative metabolism in leukemic cells as revealed by luminol-dependent chemiluminescence. As in mature monocytes, CD23 ligation induced an accumulation of intracellular cAMP in leukemic cells. These data indicate that ligation of CD23 may induce the maturation of myelomonocytic cells into monocytic-like cells.

Cyclic AMP↗
PubMed1993

Adult T-cell leukemia/lymphoma revealed by a surgically cured cardiac valve lymphomatous involvement in an Iranian woman: clinical, immunopathological and viromolecular studies.

A 60-year-old woman from the town of Mashhad in northeastern Iran developed cardiac failure due to aortic and mitral regurgitations which needed cardiac valve replacement. Histopathological study of the valves revealed a T-cell non-Hodgkin's lymphoma. Blood examination showed leukemic features with 32% of abnormal white blood cells. Human T-cell leukemia/lymphoma virus type I (HTLV-I) antibodies were present in the serum and the specific env HTLV-I sequences were detected in the DNA extracted from the valves and peripheral blood mononuclear cells (PBMC) using polymerase chain reaction technique. Clonal integration of two HTLV-I copies was found in both the valves and PBMC DNA, thus the diagnosis of adult T-cell leukemia/lymphoma (ATL) was established. In contrast to the acute life-threatening cardiac localization, our case met the diagnostic criteria of chronic ATL, this was confirmed by favorable evolution without chemotherapy during the 24 months after diagnosis. According to our knowledge, this is the first report of an isolated lymphomatous cardiac valve involvement, without other cardiac abnormalities. It seems important to underline that the patient originated from Iran where endemicity of HTLV-I has only recently been discovered.

Aortic Valve↗
PubMed1993

Modality treatment in adult stage I-II Hodgkin's disease with large mediastinal masses: study of 30 cases and review of the literature.

From January 1980 to December 1989, 30 untreated patients with supradiaphragmatic Hodgkin's disease (HD) stage IA to IIBE, presenting a mediastinal mass with mediastinal to thoracic ratio (MTR) > or = 0.33, were treated by combined modality therapy. None had staging laparotomy and the range of MTR was 0.33 to 0.60 (mean 0.43). In the entire group. MOPP chemotherapy (2 or 3 cycles) was followed by mantle irradiation of 40-45 Grays over 26 to 30 days and paraaortic-splenic pedicle irradiation of 30 Grays over 19 days. Complete remission (CR) was achieved in 26 of 30 patients (87%). The remaining 4 patients who failed to respond to initial chemotherapy received salvage chemotherapy and/or autologous bone marrow transplantation (ABMT). With a median follow-up time of 72 months (range 11 to 131 months), overall survival and disease free survival (DFS) were 86% and 78% respectively at 10 years. Five relapses were observed after 10 to 63 months of CR. Among five patients (3 relapsing and 2 failing to respond) who received intensive chemotherapy and/or ABMT, complete remission was obtained in 4 (80%). Univariate analysis of different risk factors such as age, systemic symptoms, E-lesions, histological subtype, sex, MTR and response to initial chemotherapy indicated that early response to chemotherapy was the only significant factor influencing overall survival (p < 0.001). Intensive chemotherapy with ABMT is suggested for patients failing to respond to initial chemotherapy or relapsing after combined modality treatment.

Adolescent↗
PubMed1992

Interleukin-7 is a growth factor for Sézary lymphoma cells.

Sézary syndrome is a cutaneous T cell lymphoma characterized by infiltration of the skin by CD4+ cells. These cells generally respond poorly to mitogens and T cell activators. We have studied the action of IL1 to IL4, IL6, and IL7 on the proliferation of Sézary cells from 12 patients. With the exception of IL2 and IL7, the cytokines studied had no proliferative effect on these cells. Whereas IL2 had only a low proliferative capacity (two- to threefold increase) on peripheral blood mononuclear cells, recombinant IL7 constantly induced a very significant (3-40-fold increase) proliferative response, and was used successfully to generate cell lines in three out of eight cases. Growth of Sézary cell lines was shown to be strictly dependent on IL7, and after 2-5 wk of culture presented a switch to a homogeneous phenotype CD3+4+8-7- (except for one line that remained CD7+), with a typical morphology of Sézary cells. Their tumoral origin was demonstrated by the expression of the same T cell receptor-beta gene rearrangement as the patients' T cells. Importantly, cultured normal epidermal keratinocyte supernatants could support the growth of our Sézary lines. Furthermore, the proliferative activity contained in these supernatants was completely blocked by a monoclonal anti-IL7 antibody. These results suggest that IL7 may, therefore, represent an important cytokine in the physiopathology of cutaneous T cell lymphoma.

Adult↗
PubMed1992

Macrophage activation syndromes.

The clinical and laboratory features of 47 cases of macrophage activation syndrome (MAS) were reviewed in a workshop within the Groupe Français d'Hématologie cellulaire. There was no predilection for a particular age group, while common symptoms at presentation included fever, hepatic and splenic enlargement and profound depression of blood count. Examination of bone marrow aspirates allowed diagnosis to be established in almost all cases. The most characteristic sign of MAS was the presence of well differentiated macrophages without notable cytologic abnormalities but shown to be actively ingesting haematopoietic elements. Haemophagocytic syndromes generally occur in patients who develop infections in the context of preexisting immunologic abnormalities or neoplasms. In the majority of patients evolution of the disease was regressive, once spontaneously but often after antibiotic, antiparasitic and/or antiviral treatment accompanied or not by corticotherapy and/or chemotherapy. Some regressive phases were followed by more or less long term relapse, especially in the case of associated systemic lupus erythematosus. There exists at present no explanation for the occurrence of MAS, although one may remark its association with other pathologies, in particular congenital or acquired immune deficiencies and haemopathies. Several hypotheses have been proposed to explain the appearance and evolution of the disease and at present two pathways of investigation of MAS seen to merit attention: exploration of macrophages themselves and their secretion products and exploration of lymphocytes and NK cells. The current possibilities for these investigations should lead to a greater understanding of the physiopathology of MAS and it is to be hoped that a better application of appropriate therapy will enable control of its evolution.

Adolescent↗
PubMed1990

A further characterization of B-CLL lymphocytes: phenotypic and functional studies.

The CLL-B lymphocytes are characterized by the surface expression of B cell markers (CD19, CD20, HLA-DR) and of a low intensity IgM. The presence of T antigens (CD5, CD1) may be related either to the activation stage of these cells, either to their origin from a distinct B subset. In contrast, the detection of B5, CD25, CD71 and CD38 activation markers clearly demonstrated that the B-CLL lymphocyte is a preactivated or activated cell, at various phases of the cellular cycle. Functional studies revealed that B-CLL lymphocytes are susceptible to the effects of several interleukins (BCGF(s), IL2, IFN alpha). The inhibition of the response to IL2 by IL4 has important implications for the potential use of cytokines in the management of B-CLL patients.

Antigens, Surface↗