Loss of Asxl1 leads to MDS-like disease. (A) May-Giemsa–stained PB smears prepared from representative WT (a-b) and Asxl1^−/− (c-k) mice are shown. The PB smear of Asxl1^−/− mice showed dysplastic features including hypersegmented neutrophils (c-d), bilobed and hyposegmented neutrophils (e-f) consistent with pseudo–Pelger-Huët anomaly, as well as an increased number of polychromatophilic RBCs (h-i), and Howell-Jolly body in erythrocytes (e,g). The PB smear of representative Asxl1^−/− mice showed monocytosis (j-k). (B) Parameters of PB were summarized from WT (n = 9) and Asxl1^−/− (n = 9) mice of 3 to 6 weeks of age: WBC counts (a), Hb (b), platelets (c), neutrophils (d), monocytes (e), and lymphocytes (f). *P < .05, **P < .01. (C) Hematoxylin and eosin staining of paraffin-embedded sections of femurs (a-d) and spleen (e-h) from representative WT and Asxl1^−/− mice (4 weeks old). BM: original magnification ×20 in (a) and (c), and original magnification ×100 in (b) and (d). Red arrows indicate megakaryocytes, and green arrows indicate myeloid cells. SP: original magnification ×4 in (e) and (g), and original magnification ×40 in (g) and (h). (D) Quantitation of the Gr1⁺/Mac1⁺, B220⁺, and CD4⁺/CD8⁺ cell populations. Percentage in PB, spleen, and BM cells of WT and Asxl1^−/− mice (3-5 weeks old). Data are presented as mean ± SD from 4 sets of WT and Asxl1^−/− littermates. *P < .05.