ERG variants are LOF in an in vivo leukemia model driven by ERG overexpression. (A) Enforced expression of ERG WT and WT-like variants (P116R, M219I) in mice led to the development of erythro-megakaryocytic leukemia within 220 days. (B) mCherry engraftment over time in the PB of mice. Numbering refers to 3 ERG WT mice that succumbed to disease (Figure 5A). (C) Infiltration of ERG WT/mCherry⁺ transplanted FLCs into recipient mouse BM, spleen, and PB as measured by fluorescence-activated cell sorter (FACS) analysis. Recipient mouse number 3 shown is representative of all ERG WT and WT-like (P116R, M219I) mice. (D) ERG WT and WT-like variant mice developed mCherry⁺ erythro-megakaryocytic leukemia with cKit⁺ and CD71⁺ expression. FACS plots of a representative ERG WT leukemia are shown. Nonleukemic (ie, mCherry^–) BM and spleen cells are shown as comparison.