Both radiation and chemotherapeutic drugs induce autophagy in tumor cells, and whether this contributes to cell death or survival is debated. Although a prodeath role has been reported in certain contexts, treatment-induced autophagy often exerts a prosurvival function by preventing apoptosis and delaying necrosis. Interestingly, a more specific role of autophagy has been demonstrated in certain subtypes of leukemia. The fusion oncoproteins PML-RARA and BCR-ABL, the main oncogenic drivers of acute promyelocytic leukemia and chronic myeloid leukemia (CML), respectively, have recently been identified as autophagy substrates and their degradation by autophagy shown to contribute to treatment. However, this does not seem to be a general feature of leukemic fusion oncoproteins, as we recently found that AML1-ETO, the most frequently occurring acute myeloid leukemia (AML) fusion protein, is not an autophagy substrate. Rather we demonstrate a clear prosurvival role of autophagy in this AML subtype and that addition of autophagy inhibitors in the treatment regimen might be beneficial.
Keywords: AML; AML1-ETO; BCR-ABL; PML-RARA; autophagy; chloroquine; leukemia; valproic acid; vorinostat.