Figure 7
The MCL1-selective peptidyl antagonist BIM2A kills low-passage tumor cells derived from patients with multiple myeloma. The sensitivity of 7 low-passage myeloma cell lines to the selective inhibition of BCL2, BCLXL, or MCL1 was tested using either BH3 mimetics (A) or BIM variants (B). (A) Briefly, the 7 cell lines were treated with ABT-199 (to target BCL2) or A5463 (to target BCLXL), and their sensitivity to these agents was summarized in a heat map. (B) To evaluate their sensitivity to MCL1 inhibition, the lines were also infected with lentiviral vectors that inducibly express BIM4E (inert variant), BIM2A (MCL1-selective), or BIM (to target all the prosurvival proteins) and the sensitivity summarized in a heat map. Notably, 5/7 lines were killed when MCL1 was inhibited with the MCL1-selective ligand BIM2A. The data show the mean values ± 1 SD from 3 independent experiments. ALF1-1/TK-2 and ALF-2/TK-1 were derived from the peripheral blood and bone marrow from the same patient19; they harbor the t(14;18) translocation. *The ALF-4/TK-4 cell line harbors the del17p mutation.

The MCL1-selective peptidyl antagonist BIM2A kills low-passage tumor cells derived from patients with multiple myeloma. The sensitivity of 7 low-passage myeloma cell lines to the selective inhibition of BCL2, BCLXL, or MCL1 was tested using either BH3 mimetics (A) or BIM variants (B). (A) Briefly, the 7 cell lines were treated with ABT-199 (to target BCL2) or A5463 (to target BCLXL), and their sensitivity to these agents was summarized in a heat map. (B) To evaluate their sensitivity to MCL1 inhibition, the lines were also infected with lentiviral vectors that inducibly express BIM4E (inert variant), BIM2A (MCL1-selective), or BIM (to target all the prosurvival proteins) and the sensitivity summarized in a heat map. Notably, 5/7 lines were killed when MCL1 was inhibited with the MCL1-selective ligand BIM2A. The data show the mean values ± 1 SD from 3 independent experiments. ALF1-1/TK-2 and ALF-2/TK-1 were derived from the peripheral blood and bone marrow from the same patient19 ; they harbor the t(14;18) translocation. *The ALF-4/TK-4 cell line harbors the del17p mutation.

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