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

Lamia Aït Ghezali, Atousa Arbabian, Hervé Roudot, Jean Philippe Brouland, Fanny Baran-Marszak, Evelyn Salvaris, Andrew Boyd, Hans G. Drexler, Agnes Enyedi, Remi Letestu, Nadine Varin-Blank, Bela Papp

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3 Citations (Scopus)

Abstract

Background: Endoplasmic 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. Methods: In 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. Results: We 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. Conclusion: These 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.

Original languageEnglish
Article number87
JournalJournal of Experimental and Clinical Cancer Research
Volume36
Issue number1
DOIs
Publication statusPublished - Jun 26 2017

Keywords

  • Calcium transport
  • Endoplasmic reticulum
  • Phorbol ester
  • Pre-B acute lymphoblastic leukemia
  • SERCA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Aït Ghezali, L., Arbabian, A., Roudot, H., Brouland, J. P., Baran-Marszak, F., Salvaris, E., Boyd, A., Drexler, H. G., Enyedi, A., Letestu, R., Varin-Blank, N., & Papp, B. (2017). Induction of endoplasmic reticulum calcium pump expression during early leukemic B cell differentiation. Journal of Experimental and Clinical Cancer Research, 36(1), [87]. https://doi.org/10.1186/s13046-017-0556-7