Extended Data Fig. 2: Selective BCL2 inhibitor venetoclax restores sensitivity of AML cells to AraC.
(A,B,C) Concentration response for the MOLM14 (a), U937 (b) and OCI-AML3 (c) AML cell lines upon exposure to simultaneous combinations of venetoclax (VEN) and aracytine (AraC) assessed by annexin V/7AAD staining following 24H of treatment. Scale bar: cell viability 0 to 100%. The experiment was performed 3 times and a representative example is shown. (d–f) Combination index data analysis of the concentration response data in A,B and C panels. Synergy effect correspond to a CI < 1, strong synergy effect CI < 0.3 and antagonist effect CI > 1. (n=3 independent experiments). (g) Percent of viable MOLM14, U937, KG1a and OCI-AML3 cells following treatment with venetoclax (0.5 μM) and aracytine (0.5 μM) for 24H. Values are mean ± s.e.m (n=5 independent experiments). Data analysis is by two-tailed unpaired Student’s t-test with Welch’s correction for unequal variance. P values: MOLM14, CTL/VEN **P=0.0079, CTL/AraC *P=0.0159, CTL/VEN+AraC **P=0.0079, AraC/VEN+AraC **P=0.0079; U937, CTL/VEN P=0.3095, CTL/AraC *P=0.0317, CTL/VEN+AraC **P=0.0079, AraC/VEN+AraC P=0.3095; KG1a, CTL/VEN **P=0.0079, CTL/AraC **P=0.0079, CTL/VEN+AraC **P=0.0079, AraC/VEN+AraC **P=0.0079; OCIAML3, CTL/VEN *P=0.0159, CTL/AraC P=0.3095, CTL/VEN+AraC **P=0.0079, AraC/VEN+AraC P=0.2222. (h, i) Immunoblotting of cell lines (H) and primary AML cells (I) with the indicated antibodies following 24 h of treatment with venetoclax (Cell lines: 0.5 μM; Primary cells: 50 nM) and aracytine (Cell lines: 0.5 μM, Primary cells :25 μM). The experiment was performed twice with independent experiments and a representative example is shown.
