title: Hoxa10 null animals exhibit reduced platelet biogenesis.
abstract: The transcription factor HOXA10 is an important regulator of myelopoiesis. Engineered over-expression of Hoxa10 in mice results in a myeloproliferative disorder that progresses to acute myeloid leukaemia (AML) over time, and in humans over-expression is associated with poor outcomes in AML. Here, we report that loss of Hoxa10 expression in mice results in reduced platelet count and platelet production, but does not affect clotting efficiency. About 40% fewer platelets were found in Hoxa10 null animals in comparison to wild type littermates. We found a nearly 50% reduction in the percentage of reticulated platelets in Hoxa10 null mice, suggesting deficient platelet production. Furthermore, Hoxa10 null animals recovered less efficiently from induced thrombocytopenia, supporting our hypothesis of defective platelet production. This also correlated with reduced colony formation potential of stem and progenitor cells seeded in megakaryocyte-enhancing conditions in vitro. Together, our results indicate that HOXA10 is important for megakaryopoiesis and platelet biogenesis.
authors: Chemical and Biological Engineering Department, Northwestern University, Evanston, IL, USA.|Currently at Transplant Surgery Division, Northwestern University School of Medicine, Chicago, IL, USA.
authors: Iwona M
authors: IM
authors: Konieczna
authors: Chemical and Biological Engineering Department, Northwestern University, Evanston, IL, USA.
authors: Teresa A
authors: TA
authors: DeLuca
authors: Hematology Oncology Division, Northwestern University School of Medicine, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.|Jesse Brown VA Medical Center, Chicago, IL, USA.
authors: Elizabeth A
authors: EA
authors: Eklund
authors: Chemical and Biological Engineering Department, Northwestern University, Evanston, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors: William M
authors: WM
authors: Miller
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology; D005260:Female; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D038042:Myelopoiesis / Q000502:physiology; D015539:Platelet Activation / Q000502:physiology; D010976:Platelet Count; D012156:Reticulocytes / Q000502:physiology; D013921:Thrombocytopenia / Q000209:etiology; D034061:Thrombopoiesis / Q000502:physiology*
chemical_list: D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C092119:Hoxa10 protein, mouse
keywords: HOXA10; Hoxa10; Platelets; in vivo; megakaryopoiesis; thrombopoiesis