MEP deficient for Trp53 and expressing Jak2V617F are transformed to erythroid leukemia-initiating cells. (A) Percentage of MEPs (Lin^–c-Kit⁺Sca-1^–CD34^–FcgRII/III^–) in the BM (top) and spleen (SPL) (bottom) at MPN stage (8 weeks after transplantation) in each genotype (n = 5 for each group). Data are presented as comparison with J^VF. BM: J^VFP^−/− vs J^VF, P = .0436; J^VFP^172/– vs J^VF, P = .004. SPL: WT vs J^VF, P = .0002; J^VFP^+/− vs J^VF, P = .0254; J^VFP^−/− vs J^VF, P = .0082; J^VFP^172/+ vs J^VF, P = .005; J^VFP^172/– vs J^VF, P = .0052. (B) Percentage of MEPs, GMPs (Lin^–c-Kit⁺Sca-1^–CD34⁺FcgRII/III⁺), and LSKs (Lin^–c-Kit⁺Sca-1⁺) in BM (top) and SPL (bottom) from PEL J^VFP^−/− (n = 8) and J^VFP^172/– (n = 8) mice or J^VF (n = 6) mice as control. Data are presented as comparison with J^VF. BM MEP: J^VFP^−/− vs J^VF, P = .0012; J^VFP^172/– vs J^VF, P < .0001. BM GMP: J^VFP^−/− vs J^VF, P = .0079. BM LSK: J^VFP^172/– vs J^VF, P = .0269. SPL MEP: J^VFP^−/− vs J^VF, P < .0001; J^VFP^172/– vs J^VF, P < .0001. SPL GMP: J^VFP^−/− vs J^VF, P = .005; J^VFP^172/– vs J^VF, P = .0033. SPL LSK: J^VFP^−/− vs J^VF, P = .0429; J^VFP^172/– vs J^VF, P = .0033. (C) HSPC chimerism (as a percentage) in BM of recipient mice transplanted 1:1 with J^VFP^−/− (n = 5) or J^VFP^172/– (n = 6) and J^VF BM. J^VFP^−/−: MEPs vs GMPs, P = .0008; MEPs vs LSKs, P = .0001. J^VFP^172/–: MEPs vs GMPs, P = .0018; MEPs vs LSKs, P < .0001. (D) Kaplan-Meier comparative survival analysis of recipients that were transplanted with LSKs, MEPs, and GMPs from the MPN stage of J^VFP^−/− (LSKs, n = 5; MEPs, n = 9; GMPs n = 5) or J^VFP^172/– (LSKs, n = 5; MEPs, n = 8; GMPs, n = 5) mice. P value was determined by using the log-rank test. J^VFP^−/−: MEPs vs GMPs, P = .0007; LSKs vs GMPs, P = .0017; MEPs vs LSKs, P = .0007. J^VFP^172/–: MEPs vs GMPs, P = .0006; LSKs vs GMPs, P = .0017; MEPs vs LSKs, P = .0006. (E) Genome-wide copy number profiles of flow cytometry–sorted J^VFP^−/− MEP (top panel) and GMP (bottom panel) populations after BM transplant and leukemic transformation (n = 4). (F) Genome-wide copy number profiles of flow cytometry–sorted J^VFP^172/–MEP (top panel) and GMP (bottom panel) populations after BM transplant and leukemic transformation (n = 6). Data are represented as mean ± standard error of the mean (SEM) unless otherwise indicated. The unpaired t test was used to compare the mean of 2 groups in panels A, B, and C. *P < .05, **P ≤ .01, *** P ≤ .001.