Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Academic Article uri icon

Overview

MeSH

  • Alleles
  • Animals
  • Cell Proliferation
  • Gene Deletion
  • Gene Knockout Techniques
  • Gene Silencing
  • Haploinsufficiency
  • Hematopoiesis
  • Humans
  • Leukemia, Myelomonocytic, Chronic
  • Mice

MeSH Major

  • Cell Transformation, Neoplastic
  • DNA-Binding Proteins
  • Hematopoietic Stem Cells
  • Myeloid Cells
  • Proto-Oncogene Proteins

abstract

  • Somatic loss-of-function mutations in the ten-eleven translocation 2 (TET2) gene occur in a significant proportion of patients with myeloid malignancies. Although there are extensive genetic data implicating TET2 mutations in myeloid transformation, the consequences of Tet2 loss in hematopoietic development have not been delineated. We report here an animal model of conditional Tet2 loss in the hematopoietic compartment that leads to increased stem cell self-renewal in vivo as assessed by competitive transplant assays. Tet2 loss leads to a progressive enlargement of the hematopoietic stem cell compartment and eventual myeloproliferation in vivo, including splenomegaly, monocytosis, and extramedullary hematopoiesis. In addition, Tet2(+/-) mice also displayed increased stem cell self-renewal and extramedullary hematopoiesis, suggesting that Tet2 haploinsufficiency contributes to hematopoietic transformation in vivo. Copyright © 2011 Elsevier Inc. All rights reserved.

publication date

  • July 12, 2011

has subject area

  • Alleles
  • Animals
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • DNA-Binding Proteins
  • Gene Deletion
  • Gene Knockout Techniques
  • Gene Silencing
  • Haploinsufficiency
  • Hematopoiesis
  • Hematopoietic Stem Cells
  • Humans
  • Leukemia, Myelomonocytic, Chronic
  • Mice
  • Myeloid Cells
  • Proto-Oncogene Proteins

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3194039

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2011.06.001

PubMed ID

  • 21723200

Additional Document Info

start page

  • 11

end page

  • 24

volume

  • 20

number

  • 1