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CUDC-907 combined with venetoclax in AML
results demonstrate synergy between the two drugs (CI <0.6) in all of the patient samples collected (with the excep- tion of AML#15, which did not have enough sample to assess synergy), including AML relapse samples (AML#10, AML#12, AML#13, and AML#21; Figures 2A; Online Supplementary Figure S1). In order to determine the effect of the combination on leukemic progenitor cells, colony form- ing assays were performed using primary AML patient samples. CUDC-907 alone significantly reduced colony forming capacity in all primary AML cells, with the excep-
tion of AML#19 (Figure 2B). Venetoclax also significantly reduced colony formation in the primary samples, except AML#20. Combination therapy significantly reduced colony forming capacity in all of the patient samples tested compared to individual drug treatment (Figure 2B). Normal bone marrow mononuclear cells (BMMNC) were also test- ed to determine whether healthy hematopoietic progeni- tors would be targeted by CUDC-907 and venetoclax ther- apy. These treatments did not significantly affect colony forming capacity of the normal BMMNC population
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Figure 4. Legend on next page.
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