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Previous Volume 360:2289-2301 May 28, 2009 Number 22 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Levine, R. L. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background The myelodysplastic syndromes and myeloproliferative disorders are associated with deregulated production of myeloid cells. The mechanisms underlying these disorders are not well defined.

Methods We conducted a combination of molecular, cytogenetic, comparative-genomic-hybridization, and single-nucleotide–polymorphism analyses to identify a candidate tumor-suppressor gene common to patients with myelodysplastic syndromes, myeloproliferative disorders, and acute myeloid leukemia (AML). The coding sequence of this gene, TET2, was determined in 320 patients. We analyzed the consequences of deletions or mutations in TET2 with the use of in vitro clonal assays and transplantation of human tumor cells into mice.

Results We initially identified deletions or mutations in TET2 in three patients with myelodysplastic syndromes, in three of five patients with myeloproliferative disorders, in two patients with primary AML, and in one patient with secondary AML. We selected the six patients with myelodysplastic syndromes or AML because they carried acquired rearrangements on chromosome 4q24; we selected the five patients with myeloproliferative disorders because they carried a dominant clone in hematopoietic progenitor cells that was positive for the V617F mutation in the Janus kinase 2 (JAK2) gene. TET2 defects were observed in 15 of 81 patients with myelodysplastic syndromes (19%), in 24 of 198 patients with myeloproliferative disorders (12%) (with or without the JAK2 V617F mutation), in 5 of 21 patients with secondary AML (24%), and in 2 of 9 patients with chronic myelomonocytic leukemia (22%). TET2 defects were present in hematopoietic stem cells and preceded the JAK2 V617F mutation in the five samples from patients with myeloproliferative disorders that we analyzed.

Conclusions Somatic mutations in TET2 occur in about 15% of patients with various myeloid cancers.

Source Information

From INSERM U790, Institut Gustave Roussy (F.D., S.D., C.J., A.M., J.-P.L.C., Y.L., I.P., N.C., P.D., W.V.) and Université Paris XI (F.D., S.D., A.M., J.-.P.L.C., N.C., P.D., W.V.), Villejuif; Hôpital St. Antoine, Paris (F.D., C.M., N.C.); Université Paris VI Pierre et Marie Curie, Paris (F.D., N.C.); INSERM E0210, Hôpital Necker, Paris (V.D.V., S.T., F.R., S.P.R., O.A.B.); Université René Descartes, Paris (V.D.V., O.K., F.J.D., C.L., S.P.R., F.V., M.F., O.A.B.); and Hopital Cochin, Paris; INSERM Unité 567, Centre National de la Recherche Scientifique UMR8104, Institut Cochin, Hôpital Cochin, Paris (O.K., F.J.D., C.L., M.F.); Assistance Publique–Hôpitaux de Paris, Laboratoire d'Hématologie (O.K., C.L., M.F., O.A.B.) and Unité Fonctionnelle d'Hématologie (F.J.D.), Hôpital Cochin, Paris; INSERM Unité 876, Université Bordeaux 2, Bordeaux (C.J.); and Université Paris Diderot, INSERM Unité MR944, Hôpital Saint-Louis, Paris (A.A., J.S.); — all in France.

Drs. Delhommeau, Dupont, Della Valle, and James contributed equally to this article.

Address reprint requests to Dr. Bernard at INSERM E0210, Hôpital Necker, 149 rue de Vaugirard, Paris 75015, or at olivier.bernard{at}inserm.fr.

Full Text of this Article

Related Letters:

Mutation in TET2 in Myeloid Cancers
Tefferi A., Lim K.-H., Levine R., Bernard O. A., Vainchenker W.
Extract | Full Text | PDF  
N Engl J Med 2009; 361:1117-1118, Sep 10, 2009. Correspondence

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