Calcium signaling and cell fate: how can Ca (2+)signals contribute to wrong decisions for Chronic Lymphocytic Leukemic B lymphocyte outcome?

Abstract : Ca (2+)signaling is a key regulator of B lymphocyte cell fate and defects in this signaling pathway have been reported in numerous diseases such as Chronic lymphocytic leukemia (CLL). CLL is a B cell clonal disorder characterized by the accumulation of mature monoclonal CD5 (+)B cells. Although CLL could be considered to be a proliferative disease, most circulating CLL B cells are arrested in the G0 phase of the cell cycle and present both defects in calcium (Ca (2+)) homeostasis and signaling. The Ca (2+)response to antigen ligation is heterogeneous and related, in part, to defects arising from the incapacity to respond to B cell receptor (BCR) engagement (anergy), to the expression of T cell kinases (e.g. Zap70), and to the presence of negative feedback regulation by phosphatases (e.g. SHP-1). Anergic CD5 (+)CLL B cells are characterized by an elevated basal Ca (2+)level, IgM/CD79 downregulation, a constitutive activation of BCR pathway kinases, and an activation of the nuclear factor of activated T cells (NF-AT). Based on the Ca (2+)response, patients are classified into three groups: unresponders, responders with apoptosis, and responders with entry in the cell cycle. Moreover, internal and direct interaction between leukemic BCR-HCDR3 epitopes at the plasma membrane and interaction between Bcl-2 and the IP3-receptor at the endoplasmic reticulum are also suspected to interfere with the intracellular Ca (2+)homeostasis in CLL-B cells. As a whole, the Ca (2+)pathway is emerging to play a key role in malignant CLL-B survival, disease progression, and last but not least, in the therapeutic response.
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Article dans une revue
International Journal of Developmental Biology, University of the Basque Country Press, 2014, 59 (7-9), pp.379-89
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http://hal.univ-brest.fr/hal-01282849
Contributeur : Geneviève Michel <>
Soumis le : vendredi 4 mars 2016 - 14:26:16
Dernière modification le : jeudi 11 janvier 2018 - 06:22:17

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  • HAL Id : hal-01282849, version 1
  • PUBMED : 26679951

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Marjolaine Debant, Patrice Hemon, Christophe Brigaudeau, Yves Renaudineau, Olivier Mignen. Calcium signaling and cell fate: how can Ca (2+)signals contribute to wrong decisions for Chronic Lymphocytic Leukemic B lymphocyte outcome?. International Journal of Developmental Biology, University of the Basque Country Press, 2014, 59 (7-9), pp.379-89. 〈hal-01282849〉

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