Extended Data Fig. 9: Mutant Idh2 cooperates with Ints3 loss to generate a lethal myeloid neoplasm in vivo.

a, Schematic of shRNA targeting Ints3 (shInts3) retroviral BM transplantation model. b, Flow cytometry data showing the chimerism of CD45.2⁺ versus CD45.1⁺ (top) or GFP⁺ (bottom) cells in peripheral blood at four weeks post-transplant (the percentages listed represent the percent of cells within live cells; representative results from five recipient mice). c, Composition of PBMNCs at four weeks post-transplant (n = 5 per group; mean + s.d.; represented by lines above the box. statistical significance was detected in percentage of CD11b⁺Gr1⁺ cells; by two-way ANOVA with Tukey’s multiple comparison test). d–g, Chimerism of GFP⁺ cells in peripheral blood (d) and blood counts of recipients at four weeks post-transplant (Hb (e); PLT (f); MCV (g); n = 5 per group; mean ± s.d.; one-way ANOVA with Tukey’s multiple comparison test). h, Giemsa staining of BMMNCs from moribund mice with indicated genotypes (red and yellow arrows represent blastic cells and dysplastic neutrophils, respectively; inset, representative neutrophils with abnormal segmentation; scale bar, 10 μm; original magnification, ×400; representative results from five mice per genotype). i, Flow cytometry data of BM, spleen, liver, and peripheral blood from Idh2^R140Q mice treated with shInts3 (representative results from five mice). j, Schematic of HL-60 xenograft model in which recipient mice from cohort 1 were euthanized at day 18 post-transplant and mice from cohort 2 were observed for survival analysis until end stage. k–n, Blood counts (WBC (k); Hb (l); PLT (m)) and spleen weight (n) of mice from cohort 1 at day 18 post-transplant (mean ± s.d.; n = 5 per group; a two-sided Student’s t-test). o, p, Representative flow cytometry data of BM, spleen, and peripheral blood from the recipient mice from cohort 1 (o) (the percentage represents the percent of cells within live cells) and the mean percentage of GFP⁺ cells (p) (n = 5 per group; mean + s.d.; two-way ANOVA with Sidak’s multiple comparison test). q, r, Representative flow cytometry data of BM, spleen and peripheral blood from cohort 1 (q) (the percentage represents the percent of cells within GFP⁺ live cells) and the mean percentage of hCD34⁻, hCD11b⁺ and hCD13⁺ cells (r) (n = 4 per group; mean + s.d.; two-way ANOVA with Sidak’s multiple comparison test). s, Kaplan–Meier survival analysis of recipient mice from cohort 2 (n = 5 per group; log-rank (Mantel-Cox) test (two-sided)). *P < 0.05, **P < 0.01, ***P < 0.001.

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