Fig. 7

BCL-2 dependence predicts for complete remission and undetectable minimal residue disease in validation cohort. A Paired blood samples from patients with CLL were drawn pre-treatment and after 1 week of ibrutinib therapy in a frontline iFCR phase-2 clinical trial. PBMCs from these patients were isolated and used directly for in vivo BH3-profiling. Diagram was created in BioRender. Chamberlain, S. (2025) https://BioRender.com/h74g455. B Associations between the levels of CytC release by ABT199 (BCL-2 dependence) and IGHV mutational status in baseline patients as well as association between the delta levels of CytC release by ABT199 (BCL-2 dependence) and IGHV mutational status in in vivo ibrutinib-treated patients. Positive delta values from in vivo ibrutinib group indicates further net increase in BCL-2 dependence following ibrutinib treatment in comparison to baseline screening and vice versa for negative delta values. C P value heatmap plot summarizing the P values of association between BH3 profile and various clinical outcomes. Positive P values (red) indicating higher CytC release in “neg” group for MRD or “PR” group for response. MRD - minimal residue disease, BM - bone marrow, PB - Peripheral Blood. D Boxplots showing the examples of associations between baseline or delta BCL-2 dependence (represented by ABT199) and clinical outcomes. The P values were calculated by Student’s t-test. E Boxplots showing the examples of IGHV-independent associations between baseline or delta BCL-2 dependence and clinical outcomes. The P values were calculated by two-way ANOVA tests including IGHV mutational status as an additional covariate. F Boxplot of significant associations between protein expressions of paired CLL patient samples before and after in vivo ibrutinib therapy additional cohort (n = 5). Only associations above the 10% FDR control are shown