Figure 6
Figure 6. BH3 profiling demonstrates equivalent levels of mitochondrial priming and BCL2 dependence in CLL cells with del(17p) or TP53 mutation compared with wild-type CLL. (A) BIM BH3 peptide. Lack of correlation between the del(17p) or TP53 mutation status of CLL patients on the M12-175 trial and mitochondrial priming, as assessed by percent cytochrome C loss after exposure of CLL cells to BIM BH3 peptide at 0.8 μM (P = .55). Horizontal line represents the mean. n = 8 for CLL without del(17p) or a TP53 mutation, and n = 6 for CLL with either del(17p) or TP53 mutation. (B) BAD BH3 peptide. Lack of correlation of del(17p)/TP53 mutation status and functional dependence of CLL cells on BCL2 as assessed by percent cytochrome C loss after exposure of CLL cells to BAD BH3 peptide at 80 μM (P = .83). Horizontal line represents the mean. (C) Venetoclax. Lack of correlation of del(17p)/TP53 mutation status and functional dependence of CLL cells on BCL2 as assessed by percent cytochrome C loss after exposure of CLL cell mitochondria directly to the BH3 mimetic venetoclax 1 μM used analogously to a BH3 peptide in the BH3 profiling assay (P = .99). Horizontal line represents the mean.

BH3 profiling demonstrates equivalent levels of mitochondrial priming and BCL2 dependence in CLL cells with del(17p) or TP53 mutation compared with wild-type CLL. (A) BIM BH3 peptide. Lack of correlation between the del(17p) or TP53 mutation status of CLL patients on the M12-175 trial and mitochondrial priming, as assessed by percent cytochrome C loss after exposure of CLL cells to BIM BH3 peptide at 0.8 μM (P = .55). Horizontal line represents the mean. n = 8 for CLL without del(17p) or a TP53 mutation, and n = 6 for CLL with either del(17p) or TP53 mutation. (B) BAD BH3 peptide. Lack of correlation of del(17p)/TP53 mutation status and functional dependence of CLL cells on BCL2 as assessed by percent cytochrome C loss after exposure of CLL cells to BAD BH3 peptide at 80 μM (P = .83). Horizontal line represents the mean. (C) Venetoclax. Lack of correlation of del(17p)/TP53 mutation status and functional dependence of CLL cells on BCL2 as assessed by percent cytochrome C loss after exposure of CLL cell mitochondria directly to the BH3 mimetic venetoclax 1 μM used analogously to a BH3 peptide in the BH3 profiling assay (P = .99). Horizontal line represents the mean.

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