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Resistance to apoptotic cell death1 owing to overexpression of anti-apoptotic Bcl-2 family proteins including Bcl-2, Bcl-xL or Mcl-1 is considered an interesting druggable target for the treatment of hematological malignancies including acute myeloid leukemia. In fact, BH3 mimetics2 like ABT-199 (venetoclax) 3 reverse the inhibitory function of anti-apoptotic Bcl-2 proteins. 4 Dependency on Bcl-2 family protein expression requests BH3 profiling to efficiently stratify patients potentially benefiting from ABT-199 therapy. 5 Most often, Mcl-1 is considered a main resistance factor2 and recently a first class of selective Mcl-1 inhibitors was characterized. 6 As an alternative to functional inhibitors, we previously described proteasome-dependent downregulation of Mcl-1 expression7, 8 by cardiac glycoside UNBS1450. 8–10 We hypothesize here that a combination of UNBS1450 with a BH3 mimetic would affect acute myeloid …