Mutation in TET2 in Myeloid Cancers

• Published in: The New England journal of medicine Vol. 360; no. 22; pp. 2289 - 2301
• Main Authors: Delhommeau, François, Dupont, Sabrina, Valle, Véronique Della, James, Chloé, Trannoy, Severine, Massé, Aline, Kosmider, Olivier, Le Couedic, Jean-Pierre, Robert, Fabienne, Alberdi, Antonio, Lécluse, Yann, Plo, Isabelle, Dreyfus, François J, Marzac, Christophe, Casadevall, Nicole, Lacombe, Catherine, Romana, Serge P, Dessen, Philippe, Soulier, Jean, Viguié, Franck, Fontenay, Michaela, Vainchenker, William, Bernard, Olivier A
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 28.05.2009
• Subjects: Amino Acid Sequence; Animals; Antigens, CD34; Artificial chromosomes; Biological and medical sciences; Bone marrow; Chromosomes, Human, Pair 4 - genetics; Comparative Genomic Hybridization; DNA-Binding Proteins - genetics; Fluorescence in situ hybridization; Gene Rearrangement; General aspects; Hematopoietic Stem Cells - immunology; Humans; Janus Kinase 2 - genetics; Kinases; Leukemia, Myeloid, Acute - genetics; Medical sciences; Mice; Mice, Inbred NOD; Mice, SCID; Molecular Sequence Data; Mutation; Myelodysplastic Syndromes - genetics; Myeloproliferative Disorders - genetics; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins - genetics; Sequence Deletion; Stem cells; Studies; Medicine; Genetics; Mutation; Malignant tumor; Cancer
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa0810069

This article describes mutations or deletions in TET2 in patients with a spectrum of myelodysplastic syndromes and myeloproliferative disorders. The defect was independent of the JAK2 V617F mutation in such patients. It occurs in primitive hematopoietic stem cells and is an early event in the course of the disease. Since TET2 has features of a tumor-suppressor gene, it may have an initiating role in some cases of myelodysplastic syndromes and myeloproliferative disorders. This article describes mutations or deletions in TET2 in patients with a spectrum of myelodysplastic syndromes and myeloproliferative disorders. The defect occurs in primitive hematopoietic stem cells and is an early event in the course of the disease. The myelodysplastic syndromes and myeloproliferative disorders are clonal disorders that arise in hematopoietic stem cells, 1 whereas acute myeloid leukemia (AML) can arise from stem cells or more mature progenitor cells. 2 The main feature of the heterogeneous subtypes of the myelodysplastic syndromes is ineffective hematopoiesis that affects one or several lineages. 3 In about a third of patients, the disorder progresses to AML. Some of the molecular abnormalities that are associated with specific subtypes of myelodysplastic syndromes 4 or the transformation of myelodysplastic syndromes to AML 5 have been identified, but the basis of these related syndromes remains poorly understood. 6 The myeloproliferative disorders, especially . . .