Haploinsufficiency of Asxl1 is sufficient for the development of MDS-like disease and MDS/MPN in mice. (A) May-Giemsa–stained PB smears prepared from representative adult WT (a-b) and Asxl1^+/− (c-j) mice (6-12 months old) are shown. The PB smear of Asxl1^+/− mice showed dysplastic features including bilobed and hyposegmented neutrophils with clumping chromatin consistent with pseudo–Pelger-Huët anomaly (c-d), hypersegmented neutrophils (e-f), and apoptotic neutrophils (g-h). The PB smear of representative Asxl1^+/− mice showed monocytosis (i-j). (B) Parameters of PB were summarized from young WT (n = 7) and Asxl1^+/− (3-6 weeks old, n = 10) and aged WT (n = 7) and adult Asxl1^+/− (6-12 months old, n = 18) mice: WBC counts (a), Hb (b), platelets (c), neutrophils (d), monocytes (e), and lymphocytes (f). (C-D) Hematoxylin and eosin staining of paraffin-embedded sections of spleen (C, right), liver (C, left), and femurs (D), from representative aged WT and Asxl1^+/− mice. Yellow lines represent areas containing infiltrating myeloid cells (Cg-h). Blue arrows indicate dysplastic cells (Dd). Spleen and liver: original magnification ×4 in (a), (c), (e), and (g); and original magnification ×40 in (b), (d), (f), and (h). BM: original magnification ×20 in (a) and (c), and original magnification ×100 in (b) and (d). (E) Quantitation of the percentage of Gr1⁺/Mac1⁺, B220⁺, and CD4⁺/CD8⁺ cell populations in PB, spleen, and BM of WT and Asxl1^+/− mice (6-12 months old). Data are presented as mean ± SD from 5 sets of WT and Asxl1^+/− littermates. *P < .05.