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 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

626 Citations (Scopus)

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

Fingerprint

Extramedullary Hematopoiesis
Hematopoietic Stem Cells
Haploinsufficiency
Mutation
Splenomegaly
Animal Models
Transplants
Genes
Neoplasms
Cell Self Renewal

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Moran-Crusio, K., Reavie, L., Shih, A., Abdel-Wahab, O., Ndiaye-Lobry, D., Lobry, C., ... 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

Tet2 Loss Leads to Increased Hematopoietic Stem Cell Self-Renewal and Myeloid Transformation. / Moran-Crusio, Kelly; Reavie, Linsey; Shih, Alan; Abdel-Wahab, Omar; Ndiaye-Lobry, Delphine; Lobry, Camille; Figueroa, Maria; Vasanthakumar, Aparna; Patel, Jay; Zhao, Xinyang; Perna, Fabiana; Pandey, Suveg; Madzo, Jozef; Song, Chunxiao; Dai, Qing; He, Chuan; Ibrahim, Sherif; Beran, Miloslav; Zavadil, Jiri; Nimer, Stephen D; Melnick, Ari; Godley, Lucy A.; Aifantis, Iannis; Levine, Ross L.

In: Cancer Cell, Vol. 20, No. 1, 12.07.2011, p. 11-24.

Research output: Contribution to journalArticle

Moran-Crusio, K, Reavie, L, Shih, A, Abdel-Wahab, O, Ndiaye-Lobry, D, Lobry, C, Figueroa, M, 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 2011, 'Tet2 Loss Leads to Increased Hematopoietic Stem Cell Self-Renewal and Myeloid Transformation', Cancer Cell, vol. 20, no. 1, pp. 11-24. https://doi.org/10.1016/j.ccr.2011.06.001
Moran-Crusio K, Reavie L, Shih A, Abdel-Wahab O, Ndiaye-Lobry D, Lobry C et al. Tet2 Loss Leads to Increased Hematopoietic Stem Cell Self-Renewal and Myeloid Transformation. Cancer Cell. 2011 Jul 12;20(1):11-24. https://doi.org/10.1016/j.ccr.2011.06.001
Moran-Crusio, Kelly ; Reavie, Linsey ; Shih, Alan ; Abdel-Wahab, Omar ; Ndiaye-Lobry, Delphine ; Lobry, Camille ; Figueroa, Maria ; Vasanthakumar, Aparna ; Patel, Jay ; Zhao, Xinyang ; Perna, Fabiana ; Pandey, Suveg ; Madzo, Jozef ; Song, Chunxiao ; Dai, Qing ; He, Chuan ; Ibrahim, Sherif ; Beran, Miloslav ; Zavadil, Jiri ; Nimer, Stephen D ; Melnick, Ari ; Godley, Lucy A. ; Aifantis, Iannis ; Levine, Ross L. / Tet2 Loss Leads to Increased Hematopoietic Stem Cell Self-Renewal and Myeloid Transformation. In: Cancer Cell. 2011 ; Vol. 20, No. 1. pp. 11-24.
@article{001b106545934855967319d76d74aa4d,
title = "Tet2 Loss Leads to Increased Hematopoietic Stem Cell Self-Renewal and Myeloid Transformation",
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.",
author = "Kelly Moran-Crusio and Linsey Reavie and Alan Shih and Omar Abdel-Wahab and Delphine Ndiaye-Lobry and Camille Lobry and Maria Figueroa and Aparna Vasanthakumar and Jay Patel and Xinyang Zhao and Fabiana Perna and Suveg Pandey and Jozef Madzo and Chunxiao Song and Qing Dai and Chuan He and Sherif Ibrahim and Miloslav Beran and Jiri Zavadil and Nimer, {Stephen D} and Ari Melnick and Godley, {Lucy A.} and Iannis Aifantis and Levine, {Ross L.}",
year = "2011",
month = "7",
day = "12",
doi = "10.1016/j.ccr.2011.06.001",
language = "English",
volume = "20",
pages = "11--24",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Tet2 Loss Leads to Increased Hematopoietic Stem Cell Self-Renewal and Myeloid Transformation

AU - Moran-Crusio, Kelly

AU - Reavie, Linsey

AU - Shih, Alan

AU - Abdel-Wahab, Omar

AU - Ndiaye-Lobry, Delphine

AU - Lobry, Camille

AU - Figueroa, Maria

AU - Vasanthakumar, Aparna

AU - Patel, Jay

AU - Zhao, Xinyang

AU - Perna, Fabiana

AU - Pandey, Suveg

AU - Madzo, Jozef

AU - Song, Chunxiao

AU - Dai, Qing

AU - He, Chuan

AU - Ibrahim, Sherif

AU - Beran, Miloslav

AU - Zavadil, Jiri

AU - Nimer, Stephen D

AU - Melnick, Ari

AU - Godley, Lucy A.

AU - Aifantis, Iannis

AU - Levine, Ross L.

PY - 2011/7/12

Y1 - 2011/7/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79960064353&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960064353&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2011.06.001

DO - 10.1016/j.ccr.2011.06.001

M3 - Article

C2 - 21723200

AN - SCOPUS:79960064353

VL - 20

SP - 11

EP - 24

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 1

ER -