TET2 Inactivation Results in Pleiotropic Hematopoietic Abnormalities in Mouse and Is a Recurrent Event during Human Lymphomagenesis

Cyril Quivoron, Lucile Couronné, Véronique Della Valle, Cécile K. Lopez, Isabelle Plo, Orianne Wagner-Ballon, Marcio Do Cruzeiro, Francois Delhommeau, Bertrand Arnulf, Marc Henri Stern, Lucy Godley, Paule Opolon, Hervé Tilly, Eric Solary, Yannis Duffourd, Philippe Dessen, Hélène Merle-Beral, Florence Nguyen-Khac, Michaëla Fontenay, William VainchenkerChristian Bastard, Thomas Mercher, Olivier A. Bernard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

721 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)25-38
Number of pages14
JournalCancer cell
Volume20
Issue number1
DOIs
StatePublished - Jul 12 2011

Funding

We thank Dr. R. L. Levine and Omar Abdel-Wahab for valuable help with resequencing, Dr. Paola Rivera-Munhoz and Dr. Sophie Ezine for helpful discussions, and Olivia Bawa for histopathological analysis. The work was funded by grants from INSERM, Institut National du Cancer (INCa), Ligue Nationale Contre le Cancer (LNCC), Association de Recherche contre le Cancer (ARC), Fondation Gustave Roussy and by NIH/NCI grants CA129831 and CA129831-03S1 (L.G.). C.Q. is the recipient of a fellowship from the region île de France.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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