Evaluation of BCL-XL and BCL-2 as potential determinants of in vivo venetoclax responses. Xenografts were stratified into venetoclax in vivo responders and nonresponders. (A) Microarray analysis of the BCL2 family of genes with each row representing a gene. Prosurvival genes are listed at the top (in red labels), with BCL2L1 (which encodes BCL-XL) highlighted with an arrow. There are 3 groups of proapoptotic genes, encoding BCL-2 family proteins bearing all 4 BCL-2 Homology (BH) domains (BAX/BAK-like in blue labels), the BH3 domain only (purple labels), or BH3 and BH2 domains (green labels). The colors in the heatmaps represent the relative expression per gene across all samples. Red indicates relative high expression, and blue indicates relative low expression. (B) Immunoblot analysis of BCL-2 family protein expression in all 19 xenografts. (C) Protein expression of BCL-2 family members in 19 xenografts was quantified using Versadoc and calculated relative to the expression of actin within each sample and normalized to HL-60. Each dot represents an average of 3 biological replicates of each xenograft. Groups were compared using Mann-Whitney tests. With Bonferroni correction for multiple comparisons (n = 6), P < .0083 for statistical significance.
