Loss of PRC1.1 sensitizes AML cells to BCL2 blockade. (A-B) GSEA showing decreased monocyte differentiation genes in OCI-AML2 cells expressing sgPCGF1 (A) or sgBCOR (B), relative to cells expressing sgLuc. (C) Bubble plot illustrating GSEA results, highlighting the downregulation of Beat AML venetoclax-resistant gene signatures and the upregulation of Beat AML venetoclax-sensitive gene signatures in AML cells with PCGF1 or BCOR knockout, compared with wild-type controls. (D) Boxplots showing the log₂ FC in sgRNA counts for specific genes from ACER CRISPR screen in OCI-AML2 cells, comparing venetoclax treatment to DMSO. (E) Schematic overview of the CRISPR knockout screen using the ACER library in MOLM-13 cells treated with either DMSO or venetoclax. (F) Scatterplot showing the log2 FC and negative RRA score from ACER CRISPR screen in MOLM-13 cells, comparing venetoclax treatment to DMSO. (G) Boxplots showing the log2 FC in sgRNA counts for specific genes from ACER CRISPR screen in MOLM-13 cells, comparing venetoclax treatment to DMSO. (H-J) Dose-response curves showing the viability of OCI-AML2 (H), MV4-11 (I), and MOLM-13 (J) cells expressing the indicated sgRNAs, treated for 5, 4, and 3 days, respectively, with either DMSO control or different doses of venetoclax. All cell viabilities were normalized to DMSO treatment. Calculated IC₅₀ values were shown in boxplots. FDR, false discovery rate; NEG, negative control genes; NES, normalized enrichment score; ∗∗∗P < .001; ∗∗∗∗P < .0001.