Despite high initial response rates, acute myeloid leukemia (AML) treated with the BCL-2–
selective inhibitor venetoclax (VEN) alone or in combinations commonly acquires
resistance. We performed gene/protein expression, metabolomic and methylation analyses
of isogenic AML cell lines sensitive or resistant to VEN, and identified the activation of
RAS/MAPK pathway, leading to increased stability and higher levels of MCL-1 protein, as a
major acquired mechanism of VEN resistance. MCL-1 sustained survival and maintained …

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