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. 2020 Dec 23;107(1):58–76. doi: 10.3324/haematol.2020.260331

Figure 4.

Figure 4.

Mechanisms of synergy. Interactions of anti-apoptotic and pro-apoptotic BCL-2 proteins in control and BH3 mimetic-treated cells (A to D). OCI-AML3 cells were treated with venetoclax, AZD5991, or both (dose 1: venetoclax, 100 nM and AZD5991, 10 nM; dose 2: venetoclax, 250 nM and AZD5991, 25 nM) for 24 hours (h). (A to C) Interactions of BCL-2 (A), MCL-1 (B), or BCL-XL (C) with BIM, BAX, or BAK were determined by co-immunoprecipitation (co-IP) and western blot analysis. (D) Summary of the interactions. Roles of metabolic function and leukemia-stroma interactions (E and F). (E) OCI-AML3 cells were treated with venetoclax alone or in combination with IACS-10759, BL-8040, or AZD5991 with or without mesenchymal stromal cell (MSC) co-cultures for 48 h. Cell death in CD45+ cells were determined by flow cytometry. (F) Migration (6 h) and adhesion (24 h) of BL-8040 treated-OCI-AML3 cells to MSC were measured. Migration to CXCL12 was used as a positive control and random migration as a negative control. Experiments were performed in triplicates. Results are expressed as the mean ± standard error of the mean. IgG: immunoglobulin G.