Intraclonal heterogeneity in the in vitro daunorubicin-induced apoptosis in acute myeloid leukemia

Leukemic cells from ten patients with acute myeloid leukemia (AML) were sor ted on the basis of in vitro daunorubicin (DNR) uptake. The obtained subpop ulations with high and low DNR accumulation were compared with regard to in duction of apoptosis, expression of bcl-2 and p53. Heterogeneous induction of apoptosis, confined to subpopulations with high DNR uptake, was observed . The size of the DNR-induced apoptotic fraction (4% to 16%) within a given AML blast population was determined by intracellular drug accumulation and was not related to the level of bcl-2 expression. All tested leukemic samp les displayed expression of p53 in a growth promoter orientation, i.e. PAb1 620-/PAb240+. In two samples, however, sub-populations expressing a growth suppressor orientation of p53, i.e. PAb1620+/PAb240-, were also present. Th ese subpopulations were confined to high-DNR-uptake fractions and associate d with the induction of apoptosis. We conclude that intraclonal heterogenei ty in the intracellular drug accumulation and subsequently in DNR-induced a poptosis might allow the selection of inherently drug-resistant AML clones thus contributing to relapse of of leukemia.