Usp22 deletion in Kras-driven MPN mice decreases mice survival.Usp22 mRNA (A) and USP22 protein (B) expression in bone marrow and spleen cells from KM and KMUKO mice. (C) Survival analysis of WT, UKO, KM, and KMUKO mice. (D) Body weight of 5-8-week-old mice of the indicated genotype. (E) Cell blood counts in WT, KM, and KMUKO mice at 4-7 weeks of age. (F) Hematoxylin and eosin staining of spleen, liver, and lung sections from the indicated mice. Spleen sections from KMUKO mice showed complete effacement of normal architecture by neoplastic cells and reduction of the white pulp. Liver sections from KMUKO mice were severely infiltrated by nonlymphoid cells that occurred with congestion of central veins. Lung sections from KMUKO mice presented areas of consolidation with accumulation of immature dysplastic cells and massive intra-alveolar involvement likely leading to impaired lung function. Scale bars, 100 μm. (G-H) Infiltration of immature myeloid cells in the spleen, liver, and lung in 3-4-week-old WT, KM, and KMUKO mice. *P < .05, **P < .01, ***P < .001, ****P < .0001, unpaired 2-tailed Student t test (A,D-E,H); log-rank (Mantel-Cox) test (C). BM, bone marrow; Ly, lymphocytes; Neu, neutrophils; PLT, platelets; RBC, red blood cells; WBC, white blood cells.