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CUDC-907 combined with venetoclax in AML
CUDC-907 enhances venetoclax activity through upregulation of Bim and downregulation of Mcl-1
In order to begin to elucidate the mechanism of action of combined CUDC-907 and venetoclax, we treated AML cell lines for up to 24 hours to determine when enhance- ment of apoptosis occurs. Enhancement of venetoclax- induced apoptosis by CUDC-907 was detected as early as
12 hours in MOLM-13 and MV4-11 cells and 16 hours in U937 cells (Figures 3A; Online Supplementary Figure S3A). Based on these results, AML cell lines MOLM-13 and U937 were treated with the indicated concentrations for 16 and 24 hours to determine the effects on Mcl-1, Bim, and Bcl-2 protein levels. Consistent with our previous report,1 venetoclax treatment resulted in an increase of
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Figure 6. Legend on next page.
haematologica | 2021; 106(5)
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