Roles for MSI2 and PROX1 in hematopoietic stem cell activityHope, Kristin J; Sauvageau, GuyCurrent Opinion in Hematology: July 2011 - Volume 18 - Issue 4 - p 203–207 doi: 10.1097/MOH.0b013e328347888a Hematopoiesis: Edited by Hal E. Broxmeyer Abstract Author Information Purpose of review The MSI2 and PROX1 proteins are increasingly recognized for their critical roles in the biology of primitive hematopoietic cells and for their potential contributions to leukemic pathogenesis. Here we summarize the studies that have shed light on the hematopoietic-specific roles of MSI2 and PROX1 and give an overview of the molecular mechanisms underlying their function. Recent findings In addition to a likely role in cell cycle restraint, the hematopoietic stem cell agonist MSI2 is essential for the maintenance of primitive cell fate through ensuring appropriate balance between self-renewal and differentiation. Overexpression of Msi2 can contribute to the progression of murine myeloid leukemia and in the human setting is associated with poor prognosis. Regulatory control imposed by MSI2 may be achieved partly through regulation of the Notch signaling pathway. Prox1 behaves in an opposing manner to Msi2, resulting in elevated stem cell numbers when depleted. It has a potential role in cell cycle control and may act at the level of primitive hematopoietic stem and progenitor cells as it does in other systems by directly promoting commitment and differentiation. PROX1 functions as a tumor suppressor in numerous tissue types and has been found mutated in hematopoietic cell lines and primary blood malignancies. Summary Deciphering the molecular mechanisms through which MSI2 and PROX1 affect primitive hematopoietic cell fate will provide insight into the regulation of normal hematopoiesis and facilitate better understanding of the leukemic transformation process. This will be directly applicable to the development of effective regenerative therapies and targeted leukemia treatments. Molecular Genetics of Stem Cells Laboratory, Institute of Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, Quebec, Canada Correspondence to Dr Guy Sauvageau, Molecular Genetics of Stem Cells Laboratory, Institute of Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC H3C 3J7, Canada Tel: +1 514 343 7134; e-mail: firstname.lastname@example.org © 2011 Lippincott Williams & Wilkins, Inc.