Mice transplanted with Dnmt3a-KO HSCs develop myeloid malignancies. (A) WBC counts of 2 mice transplanted with Dnmt3a-KO HSCs and 3 representative mice transplanted with WT HSCs. Error bars represent mean ± SEM. (B) Wright-Giemsa staining of bone marrow and spleen touch preps from a mouse transplanted with WT HSCs and a mouse transplanted with Dnmt3a-KO HSCs diagnosed with AML. (C) Immunophenotyping confirms donor-derived cells (CD45.2) in the bone marrow express myeloid markers (Mac1/Gr1). My, myeloid; B, B-cells; T, T-cells. (D) Wright-Giemsa–stained bone marrow touch preps from a mouse transplanted with WT HSCs and from a mouse transplanted with Dnmt3a-KO HSCs that was diagnosed with MDS; shown is a dysplastic binucleated megakaryocyte with coarse granules in the cytosol in the MDS mouse. (E) Reticulin staining of a bone marrow section from a mouse transplanted with WT HSCs, and from a mouse transplanted with Dnmt3a-KO HSCs, with black fibers indicative of fibrosis. (F) Hematoxylin and eosin staining of spleen sections from the 2 mice diagnosed with PMF demonstrating extramedullary hematopoiesis. Bars represent 20 μm (B,E-F) and 10 μm (D).