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.

journal_name

Cancer Cell

journal_title

Cancer cell

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

doi

10.1016/j.ccr.2011.06.001

subject

Has Abstract

pub_date

2011-07-12 00:00:00

pages

11-24

issue

1

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(11)00222-4

journal_volume

20

pub_type

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