Figure 1.

USP7 haploinsufficiency is enriched in the TAL1-activated T-ALL. (A) TAL1 and E-protein activities at different stages of normal hematopoiesis adapted from Sanda and Leong⁵⁵. TAL1 is active during the early stage of T-cell development but down-regulated throughout T-cell maturation. E-protein, which is negatively regulated by TAL1, shows an opposite pattern. The blue color shows the decreasing TAL1 activity in normal hematopoiesis development. The green color shows E-protein activity in normal hematopoiesis development. (B) Prevalence of USP7 mutations in the four major T-ALL subgroups with ≥ 5% incidence in the TARGET T-ALL cohort. All but one of the USP7 mutations are in the TAL1 subgroup, and the enrichment is statistically significant (***p-value = 1.1e−11 by a two-sided Fishers-exact test). Representative T-ALL subgroups are ordered by their T-cell development state. (C) Density plot of the variant allele frequency (VAF) distribution of USP7 somatic mutations.