Development of lethal MDS/MPN in the lethally irradiated Sipa1^−/− recipients. Three million normal BM CD45.1⁺ cells from 8- to 9-week-old Sipa1^+/+ mice were transplanted into lethally irradiated CD45.2⁺ young (8-10 week old) Sipa1^+/+ and Sipa1^−/− recipient mice. (A) Kaplan-Meier survival curves of the lethally irradiated Sipa1^+/+ and Sipa1^−/− recipients after transplantation. The statistic difference was determined by Logrank Mantel Cox test. (B) The total BM cellularity 9 months after the transplantation. (C) Representative H&E-stained femoral sections showed increased leukocytes infiltration in the BM from the Sipa1^−/− recipients. Scale bars represent 1.0 mm. (D) Representative H&E-stained femoral sections showed increased MKs in the BM of the Sipa1^−/− recipient mice. Scale bars represent 50 μm (black) and 25 μm (white). (E) The increased numbers of MKs in the Sipa1^−/− recipient bone sections. The data are expressed as numbers per squared millimeters. (F) The frequencies of HSPCs in the recipient BM at the endpoint of the experiments. (G) H&E-stained spleen sections of Sipa1^+/+ and Sipa1^−/− recipients 9 months after transplantation. Scale bars represent 1.0 mm for the upper panels and 50 μm for the lower panels. (H) Representative FACS profile showing gating strategy for HSPCs in spleen of Sipa1^+/+ and Sipa1^−/− recipients 7 to 9 months after transplantation. (I) Frequencies of HSPCs in spleens of the Sipa1^+/+ and Sipa1^−/− recipients. (J) Reduced mature blood cells in the PB of secondary recipients 6 months after transplantation of the spleen cells from a primary Sipa1^−/− recipient with MPN. (K) The spleen weight of the secondary recipient mice 6 months after transplantation. The statistical differences in panels B-K were determined by nonparametric Mann-Whitney U test or parametric Student t test with Welch’s correction according the data distribution. See also in supplemental Figure 4. KIT, CD117 or Proto-Oncogene C-Kit; WT, wild type.