Study of apoptosis-related responses of leukemic blast cells to in vitro anthracycline treatment

Anthracyclines trigger an apoptotic cell death but their molecular targets are not totally explored. We investigated the apoptotic response of blast c ells and lymphocytes from medullary samples of 31 de novo acute leukemia. M ononuclear cells were treated in vitro by therapeutic concentrations of eit her daunorubicin (DNR) or idarubicin (IDA) for 1 h, washed and cultured for 18 h, A multivariate analysis using flow cytometry and a CD45 gating on ly mphocytes and blast cells was performed. DNR and IDA induced a Fas enhancem ent on both leukemic and normal cells. In blast cells the DEVDases were act ivated and the caspase 3 was cleaved in relation to phosphatidyl serine exp osure, showing a caspase-dependent pathway in anthracycline-induced apoptos is. Apoptotic percentages were always higher for blast cells than for lymph ocytes, confirming that anthracycline toxicity mainly affected tumor cells. Moreover, drug-induced apoptosis was not related to spontaneous apoptosis, suggesting that variations in response intensities were due to individual variations of sensitivity rather than to programmed life span time. The apo ptotic response of P-glycoprotein-expressing blast cells was not significan t, giving biological argument for the poor prognosis of multidrug resistanc e leukemia. Finally, Fas induction and anthracycline-induced apoptosis on b last cells were significantly higher when a complete remission was achieved , thus shedding light on potential new prognostic factors in acute leukemia .