Expression de Zap-70 dans les lymphocytes périphériques de sang normal et de Leucémie Lymphoïde Chronique dans un modèle unicellulaire

Zap-70 est une protéine majeure de la signalisation intracellulaire dans les lymphocytes T et NK. Zap-70 est exprimée à tous les stades de maturation dans les lymphocytes B murins, tandis que chez l homme Zap-70 est détectée dans certaines hémopathies lymphoïdes B, dans les précurseurs B normaux, et les lymphocytes B activés.L expression de Zap-70 dans les lymphocytes B normaux, matures, périphériques chez l homme est un sujet de controverse.Pour répondre à cette question, nous avons mis au point une RT-PCR qualitative pour détecter Zap-70 dans les lymphocytes B périphériques à l échelon unicellulaire. Nos résultats sont en faveur d une absence d expression de Zap-70 dans les lymphocytes B périphériques matures. Nous mettons en évidence une hétérogénéité d expression de Zap-70 dans les lymphocytes B de LLC, ainsi que dans les lymphocytes T et NK périphériques à l échelon unicellulaire.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Induction of endoplasmic reticulum calcium pump expression during early leukemic B cell differentiation

International audienceAbstractBackgroundEndoplasmic reticulum (ER) calcium storage and release play important roles in B lymphocyte maturation, survival, antigen-dependent cell activation and immunoglobulin synthesis. Calcium is accumulated in the endoplasmic reticulum (ER) by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes). Because lymphocyte function is critically dependent on SERCA activity, it is important to understand qualitative and quantitative changes of SERCA protein expression that occur during B lymphoid differentiation and leukemogenesis.MethodsIn this work we investigated the modulation of SERCA expression during the pharmacologically induced differentiation of leukemic precursor B lymphoblast cell lines that carry the E2A-PBX1 fusion oncoprotein. Changes of SERCA levels during differentiation were determined and compared to those of established early B lymphoid differentiation markers. SERCA expression of the cells was compared to that of mature B cell lines as well, and the effect of the direct inhibition of SERCA-dependent calcium transport on the differentiation process was investigated.ResultsWe show that E2A-PBX1+ leukemia cells simultaneously express SERCA2 and SERCA3-type calcium pumps; however, their SERCA3 expression is markedly inferior to that of mature B cells. Activation of protein kinase C enzymes by phorbol ester leads to phenotypic differentiation of the cells, and this is accompanied by the induction of SERCA3 expression. Direct pharmacological inhibition of SERCA-dependent calcium transport during phorbol ester treatment interferes with the differentiation process.ConclusionThese data show that the calcium pump composition of the ER is concurrent with increased SERCA3 expression during the differentiation of precursor B acute lymphoblastic leukemia cells, that a cross-talk exists between SERCA function and the control of differentiation, and that SERCA3 may constitute an interesting new marker for the study of early B cell phenotype

Additional file 3: Figure S2. of Induction of endoplasmic reticulum calcium pump expression during early leukemic B cell differentiation

Expression profile of CD19, CD20 CD22, CD34, TdT and of β-actin in key normal early B cell populations in the mouse, adapted from the Immunological Genome project transcriptomic database. (PPTX 566 kb