CLL cells are highly primed for apoptosis and usually BCL-2 dependent, and increased priming is associated with improved clinical response and unmutated IGHV. (A) PB CLL cells were BH3 profiled by FACS (n = 30) and the level of apoptotic priming for each sample was measured by quantifying the mitochondrial depolarization induced by the BIM BH3 peptide at a 0.03μM final concentration. Patient number, as detailed in supplemental Table 1, is depicted above each corresponding level of priming. (B) Examples of BH3 profiles from 3 individual patients showing pattern of relative dependence on BCL-2, MCL-1, and BCL-XL (see supplemental Table 1 for complete depolarization data for each patient by peptide). (C) Pretreatment samples from treatment-naive patients achieving a partial response (PR) or complete response (CR) by International Workshop on Chronic Lymphocytic Leukemia 2008 criteria are more primed than samples from patients with progressive disease during or within 6 months of completing frontline CLL therapy (P = .0333). (D) BH3 profiling shows that patients with unmutated IGHV status (n = 11) are significantly more primed than patients with mutated IGHV status (n = 12; P = .0074). (E) Percentage of VH homology to germline is positively correlated with level of priming (P = .0020; Spearman r: 0.480).