Therapeutics: B cell lymphoma 2 (BCL-2; BCL2); isocitrate dehydrogenase 1 (IDH1); IDH2

Cell culture and mouse studies suggest inhibiting BCL2 could help treat IDH1- or IDH2-mutant AML. Human AML cell lines with vector-mediated expression of oncogenic IDH1 or IDH2 mutations exhibited greater sensitivity to the BCL2 inhibitor venetoclax than AML cell lines expressing both wild-type IDH1 and IDH2. In mice, venetoclax decreased engraftment of IDH1-mutant AML cells compared with vehicle. Next steps include studies to investigate whether the observed IDH mutation-driven sensitization to BCL2 inhibition can be induced in non-IDH-mutant AML cells. See BioCentury Innovations 15 (Jan. 22, 2015) ...