Enforced expression of the homeobox gene Mixl1 impairs hematopoietic differentiation and results in acute myeloid leukemia
- Author(s)
- Glaser, S; Metcalf, D; Wu, L; Hart, AH; DiRago, L; Mifsud, S; D'Amico, A; Dagger, S; Campo, C; Chan, AC; Izon, DJ; Robb, L;
- Details
- Publication Year 2006-10-31,Volume 103,Issue #44,Page 16460-16465
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- 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 Mixl1 profoundly perturbed hematopoietic lineage commitment and differentiation, giving rise to abnormal myeloid progenitors and impairing erythroid and lymphoid differentiation. Moreover, all mice reconstituted with Mixl1-transduced bone marrow developed fatal, transplantable acute myeloid leukemia with a mean latency period of 200 days. These observations establish a link between enforced Mixl1 expression and leukemogenesis in the mouse.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- mouse ' retrovirus ; Mix.1 ; granulocyte macrophage progenitor
- Publisher's Version
- https://doi.org/10.1073/pnas.0607776103
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2006-10-31 12:00:00
Last Modified: 2014-12-23 01:43:04