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

We have previously demonstrated that Ph + myeloid progenitor cells of patie nts with chronic myeloid leukemia (CML) can acquire characteristics of matu re dendritic cells (DC) following calcium mobilization with calcium ionopho re (A23187, CI). In this study we characterize the intracellular signaling pathway by which CI induces the acquisition of DC features in these leukemi c cells. CI-induced activation of CML cells is attenuated by the calcineuri n phosphatase inhibitor cyclosporin A (CsA) as well as the calmodulin (CaM) antagonist W-7. These cause ablation of both the CI-induced immunophenotyp ic expression of DC markers and immunostimulatory properties in mixed leuko cyte responses (MLR). Minimal blocking effect was observed when Ca2+/CaM ki nase II (281-301) inhibitor was added to the cultures. These findings sugge st a Ca2+-dependent mechanism for the CI-induced activation of CML cells in to antigen-presenting cells (APC), which is primarily mediated through the CaM/calcineurin pathway. (C) 2000 Elsevier Science Ltd. All rights reserved .