An effective therapy by co-targeting c-Myc and Bcl-2 for resistant acute myeloid leukemia.

We showed that genetically double-knockdown of c-Myc/Bcl-2 synergistically killed AML cells and inhibited the growth of AML cells in vivo. Mechanically, co-targeting c-Myc/Bcl-2 reciprocally abrogated over-proliferation and apoptosis resistance via synergistically impairing mitochondrial biogenesis. To extend these observations, we examined the effects of double-knockdown of c-Myc and Bcl-2 on mitochondria compared with single-knockdown of c-Myc or Bcl-2 in MOLM-13 AML cells. We performed an RNA-seq experiment to reveal global gene expression changes caused by the double-KD in MOLM-13. Indeed, the transcriptional landscape of the MOLM-13 cells changed significantly upon c-Myc and/or Bcl-2 knockdown.