New drug combination restores ability of leading treatment to signal for death of blood cancer cells

New research using human tissue samples and mouse models has found that resistance of leukemia cells to a widely prescribed drug called venetoclax occurs because of a rapid increase in the breakdown and turnover of mitochondria, structures inside the cell that help power its functions. In addition to their role in producing energy, mitochondria also tell cells to die under certain adverse conditions.

Led by scientists at NYU Langone Health and its Perlmutter Cancer Center, the study showed that mitophagy helps leukemia cells to evade the killing effects of venetoclax, a drug in a class of medications known as BH3 mimetics.

Researchers found that the levels of several genes associated with mitophagy were increased in 20 leukemia patient samples compared with normal controls. The level of these genes was even higher in samples from leukemia patients with drug resistance than in those leukemic patients who were not. Particularly notable was the increased expression of the gene for Mitofusin-2 (MFN2), which codes for a key protein in the outer mitochondrial membrane.