The DNMT3A^R882H variant drives myeloproliferation. Transduction of Dnmt3a-HET bone marrow posttransplant with control vector (MIG, n = 4), WT DNMT3A (DNMT3A, n = 7), and DNMT3A^R882H (R882H, n = 4) followed by bone marrow transplant. (A) Peripheral blood engraftment of transduced donor cells (CD45.2⁺ GFP⁺) sampled at monthly intervals posttransplant. (B) Representative flow cytometry plots of engraftment and lineage distribution of transduced donor cells in peripheral blood (B, B cells; M, myeloid; T, T cells). (C) Compiled lineage distribution of donor peripheral blood cells. (D) Frequency of phenotypically defined HSCs (Lineage⁻ c-Kit⁺ Sca-1⁺ CD48⁻ CD150⁺) in the bone marrow of recipient mice 1 year posttransplant, showing contribution of recipient-derived (CD45.1⁺), donor-derived untransduced (CD45.2⁺ GFP⁻), and donor-derived transduced cells (CD45.2⁺ GFP⁺). (E) Percentage of mature myeloid cells (Gr-1⁺ Mac-1⁺) in the bone marrow and spleen of recipient mice 1 year posttransplant. (F) Gene expression analysis of CD45.2⁺ GFP⁺ Mac-1⁺ bone marrow cells 1 year posttransplant confirmed upregulation of Meis1 and HoxA9 reported by overexpression of DNMT3A^R882H in WT mouse bone marrow cells.