Figure 1. Domain-Focused CRIPSR screening identifies UBE2T and FANCL as AML-biased dependencies.

(A) Categories of E2 and E3 domains targeted in the ubiquitination domain sgRNA library. (B) Schematic of CRISPR-Cas9 screening strategy. (C) Ubiquitination machinery dependencies ranked by the average log₂ fold-change difference comparing six AML and six non-AML cell lines in the pooled CRISPR screening. (D) Average log₂ fold-change for sgRNAs targeting UBE2T, FANCL, and ANAPC11 in the twelve screened cell lines. (E) Dependency scores of five FA genes extracted from Project Achilles (20Q2) (21,22). The boxplots indicate the distribution of dependency score (CERES; a normalized metric of gene essentiality) of five FA genes across all 769 cell lines or in the subset of 41 blood cell lines. p-value was calculated using an unpaired Student’s t-test. All sgRNA experiments were performed in Cas9-expressing cell lines.