Fig. 1

BH3-profiling overview and its correlations with clinical and genetic backgrounds in primary CLL cells. A BH3-profiling is a technique used to measure how close a cell is to the threshold of apoptosis, and to identify how dependent a cell is on certain BCL-2 family anti-apoptotic protein(s) for survival. Measurements by flow cytometry are determined based on the level of cytochrome c (CytC) release, induced by specific BH3 peptides or mimetic drug, whereby the higher the CytC is released or loss (%), the higher the dependence(s) is towards its respective anti-apoptotic protein(s). The heatmap shows peptides or mimetic drug that measures the overall apoptotic priming of cells and the specific anti-apoptotic dependences of cells. Diagrams were created either in BioRender. Chamberlain, S. (2025) https://BioRender.com/y06s314 (left panel) or Powerpoint software (heatmap). B Measurement of CytC release (%) of 73 CLL patient samples from the discovery cohort, induced by the BH3 peptides or mimetic. C Heatmap showing BH3-profiling pattern with heterogenic clinical and genetic background. The CytC values (area under curve) were centered by mean and scaled by standard deviation column-wise in order to reveal the pattern among patient samples with heterogenic clinical and genetic background. D The PCA biplot shows CLL samples (points) and BH3 peptides or mimetics (arrows) on the first two principal components (PC1 and PC2). Points represent individual CLL samples, with distances indicating similarities, while arrows show variable (BH3 peptides or mimetic) contributions, with direction and length indicating correlations and influence (strength of correlations) on the components. Closer points suggest similar samples and angles between arrows indicate variable correlations. E Boxplots showing the significant associations (nominal P value < 0.05, Student’s t-test) between principal components and patient genetic background. Tri12 – Trisomy 12, WT – wild type, M – mutated, U – unmutated, HP – highly programmed, IP – intermediately programmed or LP – lowly programmed CLL based on methylation clusters, Mut – mutated. F Significant correlations (nominal P value < 0.05, Student’s t-test) between principal components and the % baseline viabilities of the cells from CLL patient samples (% live cells) after 48-h culture in media