Loss of TET2 function worsens JAK2V617F-induced MPNs. (A) The average complete blood cell counts of recipients every 4 weeks after transplantation (4-36 weeks) (n = 10). Compared with WT mice, JAK2V617F mice and double-mutant mice showed leukocytosis and anemia at 20 weeks and thrombocytosis at 8 weeks. Compared with JAK2V617F mice, double-mutant mice showed prolonged leukocytosis. (B) Spleen weight of recipient mice at 20 to 28 weeks after transplantation (n = 10). Compared with WT mice, JAK2V617F mice and double-mutant mice showed splenomegaly. Compared with JAK2V617F mice, double-mutant mice presented with more severe splenomegaly. (C) Kaplan-Meier survival curves of WT (n = 30), TET2KD (n = 33), JAK2V617F (n = 34), and double-mutant (n = 30) mice. The overall survival (OS) of JAK2V617F mice was worse than WT mice. Compared with JAK2V617F mice, double-mutant mice had modestly shorter survival duration. (D) Histologic analysis of recipient mice at 20 to 28 weeks after transplantation. Lung, liver, BM, and spleen stained with hematoxylin and eosin (HE); BM and spleen with Gomori silver stain. TET2KD mice show minimal extramedullary hematopoiesis of lung and liver. JAK2V617F mice show moderate extramedullary hematopoiesis, abnormal megakaryocytes, and fibrosis in BM and spleen. Double-mutant mice show severe extramedullary hematopoiesis, abnormal megakaryocytes, and fibrosis in BM. (E) Sizes of megakaryocytes in BM of recipients. In each group, the size of 100 megakaryocytes was measured. Megakaryocytes in JAK2V617F mice were significantly larger. Megakaryocytes in double-mutant mice were smaller than those in JAK2V617F mice but still larger than those in WT mice. Error bars represent standard deviation. *P < .05 and **P < .01 vs WT mice; †P < .05 and ††P < .01 vs JAK2V617F mice. Hb, hemoglobin; Plt, platelets; WBC, white blood cells.