H+E staining of bone marrow, spleen, and liver, and reticulin of hMPLWT mice and hMPLW515L mice treated with vehicle or INCB16562 for 12 days. Hematoxylin and eosin (H+E) stains demonstrate reduced cellularity in the (A) bone marrow and (B) reduced myeloproliferation in the spleen of INCB16562-treated W515L mice. Enumeration of megakaryocytes per ×20 field in 5 fields from the spleens of 2 to 3 mice killed on day 12 after beginning treatment reveals significant dose-dependent decrease in number of megakaryocytes with 60 mg/kg and 120 mg/kg INCB16562 (F). (C) Liver histology reveals greatly reduced extramedullary hematopoeisis in the liver with INCB16562 treatment at either 60 mg/kg or 120 mg/kg W515L mice. Reticulin staining of marrow (D) and spleen (E) reveals a decrease in myelofibrosis with 12 days of INCB16562 treatment. *P < .05 compared with vehicle-treated mice. hMPLWT mice on the other hand, show normal bone marrow (A left panel) and splenic (B left panel) architecture with minimal fibrosis (D-E left panels), and a normal hepatic structure (D left panel). (F) Error bars denote SD.