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.
authors: Department of Pathology, NYU Cancer Institute, New York University School of Medicine, NY 10016, USA.
authors: Kelly
authors: K
authors: Moran-Crusio
authors: Linsey
authors: L
authors: Reavie
authors: Alan
authors: A
authors: Shih
authors: Omar
authors: O
authors: Abdel-Wahab
authors: Delphine
authors: D
authors: Ndiaye-Lobry
authors: Camille
authors: C
authors: Lobry
authors: Maria E
authors: ME
authors: Figueroa
authors: Aparna
authors: A
authors: Vasanthakumar
authors: Jay
authors: J
authors: Patel
authors: Xinyang
authors: X
authors: Zhao
authors: Fabiana
authors: F
authors: Perna
authors: Suveg
authors: S
authors: Pandey
authors: Jozef
authors: J
authors: Madzo
authors: Chunxiao
authors: C
authors: Song
authors: Qing
authors: Q
authors: Dai
authors: Chuan
authors: C
authors: He
authors: Sherif
authors: S
authors: Ibrahim
authors: Miloslav
authors: M
authors: Beran
authors: Jiri
authors: J
authors: Zavadil
authors: Stephen D
authors: SD
authors: Nimer
authors: Ari
authors: A
authors: Melnick
authors: Lucy A
authors: LA
authors: Godley
authors: Iannis
authors: I
authors: Aifantis
authors: Ross L
authors: RL
authors: Levine
mesh_terms: D000483:Alleles; D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000378:metabolism; D049308:Dioxygenases; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D020868:Gene Silencing; D057895:Haploinsufficiency / Q000235:genetics; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000473:pathology; D051379:Mice; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human; C551914:Tet2 protein, mouse