Depletion of megakaryocytes attenuated the MPN phenotype induced by MPLW515L. c-Kit+ bone marrow cells of IDTR+/- mice with or without PF4Cre were transduced with retroviruses carrying MPLW515L. Injection of diphtheria toxin (DT) was initiated on day 28 post-transplant. Depletion of megakaryocytes by DT reduced platelet and white count (A, B), decreased spleen weight (C) and reduced megakaryocyte and erythroid cell infiltration in the spleen (D). *, p<0.05, **, p<0.01.