TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis

Cancer Cell. 2011 Jul 12;20(1):25-38. doi: 10.1016/j.ccr.2011.06.003. Epub 2011 Jun 30.


Loss-of-function mutations affecting one or both copies of the Ten-Eleven-translocation (TET)2 gene have been described in various human myeloid malignancies. We report that inactivation of Tet2 in mouse perturbs both early and late steps of hematopoiesis including myeloid and lymphoid differentiation in a cell-autonomous manner, endows the cells with competitive advantage, and eventually leads to the development of malignancies. We subsequently observed TET2 mutations in human lymphoid disorders. TET2 mutations could be detected in immature progenitors endowed with myeloid colony-forming potential. Our results show that the mutations present in lymphoid tumor cells may occur at both early and later steps of lymphoid development and indicate that impairment of TET2 function or/and expression predisposes to the development of hematological malignancies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • Cell Lineage
  • DNA-Binding Proteins / genetics*
  • Dioxygenases
  • Gene Silencing*
  • Hematopoiesis*
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology
  • Homeostasis
  • Humans
  • Lymphoma / metabolism
  • Lymphoma / pathology*
  • Mice
  • Models, Animal
  • Mutation / genetics
  • Myeloid Cells / metabolism
  • Myeloid Cells / pathology
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology*
  • Proto-Oncogene Proteins / genetics*


  • Antigens, CD34
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Dioxygenases
  • TET2 protein, human
  • Tet2 protein, mouse