Artikel ; Online: In aggressive forms of mastocytosis, TET2 loss cooperates with c-KITD816V to transform mast cells.
2012 Band 120, Heft 24, Seite(n) 4846–4849
Abstract: Although a role for oncogenic KIT in driving mast cell disease is clear, the mechanisms driving the multiple phenotypic and clinical manifestations of this disorder are not well elucidated. We now show, using a large cohort of mastocytosis patients, ... ...
| Abstract | Although a role for oncogenic KIT in driving mast cell disease is clear, the mechanisms driving the multiple phenotypic and clinical manifestations of this disorder are not well elucidated. We now show, using a large cohort of mastocytosis patients, including an almost equal number of aggressive and nonaggressive cases of systemic mastocytosis, that in contrast to the oncogenic KITD816V, TET2 mutation statistically associates with aggressive forms of the disease. By infecting primary murine bone marrow-derived mast cells with KITD816V, we also observe a significant and competitive growth advantage for KITD816V in Tet2-nullizygous compared with wild-type cells. TET2-deficient cells display increased proliferation and can survive in the absence of cytokines. Taken together, these data demonstrate a oncogenic cooperation in mast cells and reveal TET2 mutation as a potential marker to diagnose and predict severe forms of mastocytosis. |
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| Mesh-Begriff(e) | Adult ; Aged ; Aged, 80 and over ; Amino Acid Substitution ; Animals ; Bone Marrow Cells/metabolism ; Cell Survival/genetics ; Cell Transformation, Neoplastic/genetics ; Cells, Cultured ; Cohort Studies ; DNA-Binding Proteins/genetics ; Female ; Humans ; Male ; Mast Cells/metabolism ; Mast Cells/pathology ; Mastocytosis/genetics ; Mastocytosis/pathology ; Mice ; Mice, Knockout ; Middle Aged ; Mutation ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins c-kit/genetics ; Time Factors ; Transfection | ||||||||||
| Chemische Substanzen | DNA-Binding Proteins ; Proto-Oncogene Proteins ; TET2 protein, human (EC 1.13.11.-) ; Tet2 protein, mouse (EC 1.13.11.-) ; Proto-Oncogene Proteins c-kit (EC 2.7.10.1) | ||||||||||
| Sprache | Englisch | ||||||||||
| Erscheinungsdatum | 2012-10-16 | ||||||||||
| Erscheinungsland | United States | ||||||||||
| Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 80069-7 | ||||||||||
| ISSN | 1528-0020 ; 0006-4971 | ||||||||||
| ISSN (online) | 1528-0020 | ||||||||||
| ISSN | 0006-4971 | ||||||||||
| DOI | 10.1182/blood-2011-12-397588 | ||||||||||
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| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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