• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation.

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.

Pubmed ID: 21723200

Authors

  • Moran-Crusio K
  • Reavie L
  • Shih A
  • Abdel-Wahab O
  • Ndiaye-Lobry D
  • Lobry C
  • Figueroa ME
  • Vasanthakumar A
  • Patel J
  • Zhao X
  • Perna F
  • Pandey S
  • Madzo J
  • Song C
  • Dai Q
  • He C
  • Ibrahim S
  • Beran M
  • Zavadil J
  • Nimer SD
  • Melnick A
  • Godley LA
  • Aifantis I
  • Levine RL

Journal

Cancer cell

Publication Data

July 12, 2011

Associated Grants

  • Agency: NCI NIH HHS, Id: 1R01CA138234-01
  • Agency: NCI NIH HHS, Id: 5 P30CA16087-31
  • Agency: NCI NIH HHS, Id: 5P30CA16087-31
  • Agency: NCI NIH HHS, Id: CA129831
  • Agency: NCI NIH HHS, Id: CA129831-03S1
  • Agency: NIA NIH HHS, Id: F31-AG039991
  • Agency: NCI NIH HHS, Id: P30 CA016087-30
  • Agency: NCI NIH HHS, Id: R01 CA105129
  • Agency: NCI NIH HHS, Id: R01 CA105129-07
  • Agency: NCI NIH HHS, Id: R01 CA133379
  • Agency: NCI NIH HHS, Id: R01 CA133379-04
  • Agency: NCI NIH HHS, Id: R01 CA149655
  • Agency: NCI NIH HHS, Id: R01 CA149655-03
  • Agency: NCI NIH HHS, Id: R01CA105129
  • Agency: NCI NIH HHS, Id: R01CA133379
  • Agency: NCI NIH HHS, Id: R01CA149655
  • Agency: NIGMS NIH HHS, Id: R01GM088847
  • Agency: NCI NIH HHS, Id: R21CA141399
  • Agency: NCI NIH HHS, Id: U54CA143798-01
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • 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