UTX expression is critical for HSPC cell migration and normal hematopoiesis. (A) Tamoxifen treatment of adult UTX^FDC/FDC female mice results in significant weight loss compared with nontreated animals. Tamoxifen treatment had no effect on the body weight of UTX^FDC/Y male mice. (B) Treatment of adult UTX^FDC/FDC female mice results in a significant increase of spleen weight compared with nontreated animals. Tamoxifen treatment had no effect on spleen weight of UTX^FDC/Y male mice. (C) Treatment of adult UTX^FDC/FDC female mice results in anemic bones and a significant increase of spleen size compared with nontreated animals. Representative images of spleen and tibia are shown. (D) Bone marrow sections from adult UTX^FDC/FDC female mice showed disturbed cell distribution with concomitant pronounced myeloid dysplasia. Images display an increased number of megakaryocytes with abnormal nuclear lobation (black arrowhead) and granulocytes with nuclear hyposegmentation (white arrowhead) in comparison with sections from UTX^FD/FD female mice. Representative images from hematoxylin and eosin staining are shown. (E) Example of metaphase spreads from SKY analysis of UTX^FDC/FDC bone marrow cells is given. The following chromosomal aberrations were evident: T(14B;16B?) and double-strand break of chromosome 17 (white arrows). (F) Spleens from adult UTX^FDC/FDC female mice showed increased extramedullary hematopoiesis and megakaryocytes with abnormal nuclear lobation (black arrowhead). Representative images from chloracetate-esterase staining are shown. (G) Significantly reduced gene expression levels of the erythroid and megakaryocytic lineage-specific transcription factors LYL-1, SCL, and GATA-1 were observed in the bone marrow of UTX^FDC/FDC mice compared with UTX^FD/FD female mice. (H) HSPCs from Tamoxifen-treated adult UTX^FDC/FDC female mice demonstrated a significantly reduced migration potential compared with HSPCs from nontreated animals. Tamoxifen treatment of UTX^FDC/Y male mice did not influence the migration rate of HSPCs. (I) Bone marrow cells from Tamoxifen-treated adult UTX^FDC/FDC female mice demonstrated a significantly reduced number of CFUs and an altered composition of CFUs compared to cells from UTX^FD/FD, UTX^FD/Y, and UTX^FDC/Y animals, respectively. *P < .05, **P < .01. BFU-E, burst forming unit–erythroid; CFU-GM, granulocyte-macrophage progenitor; CFU-M, macrophage; ns, not significant; Pre-B, lymphoid progenitors.