HSC-restricted activation of Srsf2^P95H/+causes MDS/MPN. (A) Kaplan-Meier plot of disease-free survival for the hScl-CreER (blue) and R26-CreER (gray) models. (B) PB leukocyte counts and lineage distribution. (C) PB hemoglobin levels. (D) PB neutrophils from a control (age-/treatment-matched hScl-CreER R26eYFP Srsf2^+/+ littermate) and 3 independent hScl-CreER R26eYFP Srsf2^P95H/+ animals; May-Grunwald Giemsa stain. (E) Number of PB monocytes and neutrophil precursors over time after tamoxifen (n = 6-13 per genotype per time point; based on Ly6c/CD11b stain). (F) BM cellularity and number of granulocytes and monocytes per femur. (G) BM myeloid (Mac-1/Gr-1) and B lymphoid (B220/immunoglobulin M [IgM]) populations in BM. (H) Number of phenotypic LT-HSCs, ST-HSCs, and MPPs per femur and myeloerythroid progenitors per femur. (I) Number of granulocytes and monocytes per spleen. (J) CD45RB isoform expression on splenocytes. (K) PB CD45 chimerism from secondary transplantation of whole BM into lethally irradiated recipients (black circle = littermate control; blue squares = moribund Srsf2^P95H/+); each line represents reconstitution of an individual recipient (n = 4); PB eYFP percentage in the CD45.2⁺ cells; PB leukocyte counts, representative PB FACS from recipients, and quantitation of lineage output from the CD45.2 population (4 weeks post–BM transplantation [BMT]). Presented as mean ± standard error of the mean. Student t test, with multiple comparisons correction (for panel E). *P < .05, **P < .01, ***P < .001.