Sfpi1 haploinsufficiency cooperates with Sox4 to induce myeloid leukemia development. (A) A schematic diagram showing the bone marrow transduction and transplantation assay using Sfpi1^KO/+ or Sfpi1^+/+ bone marrow cells. (B) All-cause mortality curve is shown. The cohort of mice that received MSCV-Sox4 infected bone marrow cells from Sfpi1^KO/+ mice is labeled as Sox4/Sfpi1 (32 animals). Mice that received MSCV-Sox4 infected bone marrow cells from wild-type C57/Bl/6J mice are labeled as Sox4/Wt group (28 animals). The Neo/Sfpi1 group contains mice that received marrow cells from Sfpi1^KO/+ mice infected with MSCV (16 animals). Myeloid leukemias developed between 3 and 11 months. Statistical significance between groups using the log-rank test is: Neo/Sfpi1 versus Sox4/Wt (P < .001), Sox4/Wt versus Sox4/Sfpi1 (P < .001), Neo/Sfpi1 versus Sox4/Sfpi1 (P < .001). (C) H&E staining of bone marrow from a mouse of the Sox4/Sfpi1 cohort showing myeloid leukemia (original magnification ×40). (D) H&E staining of bone marrow from the same leukemic mouse showing myeloid blasts (original magnification ×400). (E) H&E staining of a spleen section from same mouse showing myeloid leukemia (original magnification ×40). (F) Representative liver section of the same mouse in panels C and D stained positive for myeloperoxidase (original magnification ×40). (G) Myeloperoxidase staining of bone marrow from a secondary transplantation is showing myeloid leukemia (original magnification ×40). (H) Top part of the picture shows a splenic tumor (myeloid leukemia, weight 0.16 g) day 26 of secondary transplantation compared with WT control spleen (bottom part of picture, weight 0.048 g). Images were captured on an Olympus Bx41 microscope, objective UPlan FI 40×/0.75 ∞/0.17, with an adaptor U-TV0.63XC using a digital camera Q-imaging Micropublisher Version 5.0 RTV (Q imaging) using Q-Capture Version 3.1.