Myelomonocytic expansion and myelodysplasia in Cux1^lowmice. Representative morphology images are shown from mice at the time of euthanization because of disease. (A) Wright-Giemsa staining of the peripheral blood in (Ai) Ren and (Aii-Av) Cux1^low mice. (Aii) The increased white blood cell count is primarily composed of mature granulocytes (arrowheads), monocytes (arrow), and (Aiii) occasional circulating myeloblasts (arrows). (Aiv) Dysplasia in the granulocyte lineage as evidenced by pseudo Pelger-Huet anomaly (arrows). (Av) Red blood cells in Cux1^low mice have anisopoikilocytosis: (1) macrocyte; (2) microcyte; (3) target cell; (4) spherocyte; (5) tear drop cell; (6) and red cell fragment. (7) Polychromatophilic reticulocyte. (8) Giant platelet. (B) Touch preparation of Cux1^low spleen shows erythroid dysplasia, including (Bi) binucleated erythroblast (arrow) and nuclear budding (arrowheads), (Bii) nuclear budding, and (Biii) abnormal nuclear contours. (Biv) Pseudo Chediak-Higashi granule in a maturing granulocyte. (C) H&E of Cux1^low BM demonstrates numerous megakaryocytes. Nine megakaryocytes (yellow arrowheads) are shown in a single high-power field, several of which are atypically small, with hypolobation and condensed, hyperchromatic nuclei. (D) Compared with Ren, Cux1^low spleen H&E staining demonstrates complete effacement of normal splenic architecture with expansion of red pulp and increased megakaryocytes. White pulp is outlined with a yellow dashed line for clarity. There is a small portion of residual white pulp in the bottom left corner of the Cux1^low spleen (D, middle panel). Micromegakaryocytes are present, as well as megakaryocytes with hypolobation, abnormally widely spaced nuclear lobes, and hyperchromatic nuclei. H&E staining shows a myelomonocytic cell infiltrate in the following organs of Cux1^low mice: (E) lymph nodes; (F) liver periportal and sinusoidal areas; (G) kidney; and (H) lung. Images were taken with a Zeiss Axioskop microscope.