Determination of caspase-3 activation fails to predict chemosensitivity in primary acute myeloid leukemia blasts

Abstract

Abstract Background Ex-vivo chemosensitivity tests that measure cell death induction may predict treatment outcome and, therefore, represent a powerful instrument for clinical decision making in cancer therapy. Such tests are, however, work intensive and, in the case of the DiSC-assay, require at least four days. Induction of apoptosis is the mode of action of anticancer drugs and should, therefore, result in the induction of caspase activation in cells targeted by anticancer therapy. Methods To determine, whether caspase activation can predict the chemosensitivity, we investigated enzyme activation of caspase-3, a key executioner caspase and correlated these data with chemosensitivity profiles of acute myeloid leukemia (AML) blasts. Results There was, however, no correlation between the ex-vivo chemosensitivity assessed by measuring the overall rates of cell death by use of the DiSC-assay and caspase-3 activation. Conclusion Thus, despite a significant reduction of duration of the assay from four to one day, induction of apoptosis evaluated by capase-3 activity does not seem to be a valid surrogate marker for chemosensitivity.