Tet2 Loss Leads to Increased Hematopoietic Stem Cell Self-Renewal and Myeloid Transformation

Kelly Moran-Crusio, Linsey Reavie, Alan Shih, Omar Abdel-Wahab, Delphine Ndiaye-Lobry, Camille Lobry, Maria E. Figueroa, Aparna Vasanthakumar, Jay Patel, Xinyang Zhao, Fabiana Perna, Suveg Pandey, Jozef Madzo, Chunxiao Song, Qing Dai, Chuan He, Sherif Ibrahim, Miloslav Beran, Jiri Zavadil, Stephen D. NimerAri Melnick, Lucy A. Godley, Iannis Aifantis, Ross L. Levine

Research output: Contribution to journalArticle

671 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)11-24
Number of pages14
JournalCancer Cell
Volume20
Issue number1
DOIs
StatePublished - Jul 12 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Moran-Crusio, K., Reavie, L., Shih, A., Abdel-Wahab, O., Ndiaye-Lobry, D., Lobry, C., Figueroa, M. E., Vasanthakumar, A., Patel, J., Zhao, X., Perna, F., Pandey, S., Madzo, J., Song, C., Dai, Q., He, C., Ibrahim, S., Beran, M., Zavadil, J., ... Levine, R. L. (2011). Tet2 Loss Leads to Increased Hematopoietic Stem Cell Self-Renewal and Myeloid Transformation. Cancer Cell, 20(1), 11-24. https://doi.org/10.1016/j.ccr.2011.06.001