(A) BM cells from Dnmt3a^–/– mice were transplanted into lethally irradiated C57BL/6 mice, and 6 weeks after transplantation, mice were treated with vehicle or the PI3K αβ inhibitor (Bay1082439; 75 mg/kg body weight) for 21 days. (B) BM bearing Dnmt3a^–/– cells from mice treated with vehicle or the PI3K αβ inhibitor were subjected to Western blot analysis to analyze pAKT and total AKT protein levels. Numbers at the top represent the number of mice used for these experiments. (C and D) Images of spleens and livers from vehicle- and drug-treated mice and respective quantitative assessment of liver and spleen weights from vehicle- or drug-treated mice. n = 5–6, mean ± SEM, unpaired t test (2-tailed), ****P < 0.00005. (E and F) Peripheral blood smears and BM cytospin preparations showing reduced dysplasia of myeloid and erythroid lineage cells in PI3K αβ inhibitor–treated mice compared with vehicle group. Arrows in blood smears indicate segmented neutrophils. Yellow circle indicates myeloblasts, and green circles/green arrows indicate metamyelocytes. PB smear images shown at 100× magnification (E). Scale bar: 60 μm (F). (G) Representative images for H&E-stained sections of BM. Scale bar: 50μm (H) H&E-stained liver sections showing increased sinusoidal spaces with reduced immature myeloid cell infiltration in in PI3Kαβ inhibitor treatment condition compared with vehicle treatment. Immature myeloid precursor Metamyelocytes (yellow circle) and proliferating myeloid cells (green circles) in vehicle-treated mice are indicated. Scale bar: 50 μm (I) H&E-stained spleen sections showing reduced immature myeloid cell infiltration in the PI3Kαβ inhibitor treatment condition compared with vehicle treatment. Yellow circle indicates dysplastic megakaryocyte. More proliferating myeloid cells in vehicle-treated mice (green circles indicate mitotic figures of myeloproliferation). Scale bar: 50 μm (upper panel), 1,000 μm (lower panel).