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Figure 5. Combined inhibition of BCL-2 and MCL-1 synergisti- cally induces apoptosis in primary acute myeloid leukemia (AML) cells and AML stem/progenitor cells under mesenchy- mal stromal cell co-culture conditions. Primary acute myeloid leukemia (AML) cells co-cultured with mesenchymal stromal cellc (MSC) were treated with venetoclax (VEN), AZD5991, AZD4573, VEN plus AZD5991, or VEN plus AZD4573 for 48 hours (h). The apoptosis of blast cells and stem/progenitor cells were assessed by flow cytometry. (A) Half maximal effec- tive concentration (EC50) values of venetoclax alone or com- bined with AZD5991 or AZD4573, of AZD5991 alone or com- bined with venetoclax and of AZD4573 alone or combined with venetoclax in blast cells and stem/progenitor cells from individual patient samples are shown. Samples lacking the indicated cell populations or that had excessively high sponta- neous apoptosis are not represented. *>3,000 nM. (B) Mutations, venetoclax treatment status, and cytogenetics/risk category of each patient from whom primary AML samples were obtained. HR: complex cytogenetics and high risk; IR: intermediated risk.
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