Enforced expression of the homeobox gene Mixl1 impairs hematopoietic differentiation and results in acute myeloid leukemia

Abstract

Mixl1, the sole murine homologue of the Xenopus Mix/Bix family of homeobox transcription factors, is essential for the patterning of axial mesendodermal structures during early embryogenesis. Gene targeting and overexpression studies have implicated Mixl1 as a regulator of hematopoiesis arising in differentiating embryonic stem cells. To assess the role of Mixl1 in the regulation of adult hematopoiesis, we overexpressed Mixl1 in murine bone marrow using a retroviral transduction/transplantation model. Enforced expression of Mixli1 profoundly perturbed hematopoietic lineage commitment and differentiation, giving rise to abnormal myeloid progenitors and impairing erythroid and lymphoid differe..