Calcium ionophore activation of chronic myelogenous leukemia progenitor cells into dendritic cells is mediated by calcineurin phosphatase

Friederike H.C. Engels, Daniel Kreisel, Mark B. Faries, Isabelle Bedrosian, Gary K. Koski, Peter A. Cohen, Brian J. Czerniecki

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

We have previously demonstrated that Ph+ myeloid progenitor cells of patients with chronic myeloid leukemia (CML) can acquire characteristics of mature dendritic cells (DC) following calcium mobilization with calcium ionophore (A23187, CI). In this study we characterize the intracellular signaling pathway by which CI induces the acquisition of DC features in these leukemic cells. CI-induced activation of CML cells is attenuated by the calcineurin phosphatase inhibitor cyclosporin A (CsA) as well as the calmodulin (CaM) antagonist W-7. These cause ablation of both the CI-induced immunophenotypic expression of DC markers and immunostimulatory properties in mixed leukocyte responses (MLR). Minimal blocking effect was observed when Ca2+/CaM kinase II (281-301) inhibitor was added to the cultures. These findings suggest a Ca2+-dependent mechanism for the CI-induced activation of CML cells into antigen-presenting cells (APC), which is primarily mediated through the CaM/calcineurin pathway. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)795-804
Number of pages10
JournalLeukemia Research
Volume24
Issue number10
DOIs
StatePublished - Oct 1 2000

Keywords

  • Ca/calmodulin kinase II (281-301)
  • Calmodulin/calcineurin pathway
  • Chronic myelogenous leukemia (CML)
  • Cyclosporin A (CsA)
  • Dendritic cells (DC)
  • Inhibitory effect
  • Myeloid progenitor cells
  • W-7

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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