Figure 1.

Whole-genome CRISPR/Cas9 screens of acute lymphoblastic leukemia (ALL) cell lines identify ALL essential genes. (A) Schema of B-ALL screening pipeline. (B) Significant genes set intersection of 7 B-ALL cell line CRISPR screen results with UpSet, “Broad” and “Sanger” essential gene list at false discovery rate (FDR) <0.05. The intersections with more than 5 genes are shown. (C) Overlap between B-ALL essential (>4/7 cell lines, FDR <0.05) genes, “Broad” and “Sanger” core essential genes. (D) Representative Volcano plot of 697 cells CRISPR screen results with FDR <0.05. B-ALL-known dependencies and B-ALL-enriched essential genes are highlighted in dark blue and in light blue, respectively. Genes regulating ferroptosis induction are highlighted in orange) Gene Network Analysis of B-ALL-enriched essential genes where nodes represent genes and edges represent proteinprotein interactions between genes. Node color represents the number of ALL cell lines essential for the given gene. (F) Log₂ fold change distribution of single-giude RNA (sgRNA) in the 7 ALL screened cell lines. sgRNA log₂ fold change for ferroptosis related genes are illustrated at bottom of the panel. VAX1, negative control. TP53 was enriched in several B-ALL cell lines. Tf: final time points; M.O.I: multiplicity of infection.