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Human chronic myelogenous leukemia K562 cells are relatively resistant to
the anti-metabolite cytosine arabinoside (Ara-C) and, when treated with Ara-C,
they differentiate into erythrocytes without undergoing apoptosis. In this study
we investigated the mechanism by which Ara-C induces K562 cells to
differentiate. We first observed that Ara-C-induced differentiation of these
cells is completely inhibited by the radiosensitizing agent caffeine, an
inhibitor of ATM and ATR protein kinases. We next found that Ara-C activates
Chk1 and Chk2 in the cells, and that the activation of Chk1, but not of Chk2,
was almost completely inhibited by caffeine.
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