Equal number of bone marrow mononuclear cells from CD45.1-expressing BoyJ mice and CD45.2 expressing Tet2^–/–:Flt3^ITD/ITD AML mice were mixed and transplanted to lethally irradiated F1 recipients that expresses both CD45.1 and CD45.2. 6 weeks after transplant peripheral blood engraftment was analyzed. Mice were treated orally with either vehicle or HSN748 at 20 mg/kg 5 times a week. HSN748 treatment of these mice reduces peripheral leukemic burden. (A) WBC, neutrophil,and monocyte counts. HSN748 treatment reduces splenomegaly. (B) Spleen pictures, quantification data for spleen weight in the middle panel and reduction of leukemic cells (CD45.1) with significant increase in normal cells (CD45.1⁺) in the right-side panel. (C) the representative flow profiles of erythroid differentiation in bone marrow from vehicle and HSN748-treated groups. HSN748 treatment induces differentiation of erythroid cells in bone marrow as demonstrated by increase in mature Ter119⁺ single-positive cells in the bone marrow of HSN748-treated mice compared with vehicle-treated group (right side panel). (D) shows the representative flow profiles of CD11b/Gr1 cells. HSN748 treatment induces differentiation of myeloid cells in the bone marrow as shown by increase in the frequency of mature CD11b/Gr1 double-positive cells and a decrease in the frequency of immature CD11b^–/Gr1⁺ single-positive population compared with vehicle-treated group (middle panel) and a reduction in the frequency of immature CD11b^–/Kit⁺ leukemic cells (right side panel). (E) The representative flow profiles of Lin^– Sca1⁺Kit⁺ (LSK) cells. (F) shows the quantification data of frequency of lineage negative cells (left side panel) and total frequency of lin^– Kit⁺ myeloid progenitors (right side panel) with insignificant effect on LSK total frequency (middle panel) on HSN748 treatment. Data represents median with interquartile range by 2-tailed Welch’s t test (n = 6 in each group ***P < 0.001, *P < 0.05).