2009.06.29 – Analysis of the Ten-Eleven Translocation (TET)2 gene in familial myeloproliferative neoplasms

Blood First Edition Paper, prepublished online June 29, 2009; DOI 10.1182/blood-2009-01-197525.
Submitted January 12, 2009
Accepted June 14, 2009

2009.06.29 – Analysis of the Ten-Eleven Translocation (TET)2 gene in familial myeloproliferative neoplasms

Cecile Saint-Martin, Gwendoline Leroy, Francois Delhommeau, Gerard Panelatti, Sabrina Dupont, Chloe James, Isabelle Plo, Dominique Bordessoule, Christine Chomienne, Andre Delannoy, Alain Devidas, Martine Gardembas-Pain, Francoise Isnard, Yves Plumelle, Olivier Bernard, William Vainchenker, Albert Najman, and Christine Bellanne-Chantelot*

Department of Genetics, AP-HP Groupe Hospitalier Pitie-Salpetriere, Universite Pierre et Marie Curie-Paris 6, Paris, France
INSERM, U790, Institut Gustave Roussy, Villejuif, France
Department of Internal Medicine, CHU de Fort de France, Fort de France, France
INSERM, U876, Bordeaux, France
Department of Hematology, CHU de Limoges, Limoges, France
Department of Cellular Biology, AP-HP Hopital Saint Louis, Universite Denis Diderot-Paris 7, Paris, France
Department of Internal Medicine, Universite Catholique de Louvain, Leuven, Belgium
Department of Hematology, CH Sud-Francilien, Corbeil-Essonnes, France
Department of Hematology, CHU d’Angers, Angers, France
Department of Hematology, AP-HP Hopital Saint Antoine, Universite Pierre et Marie Curie-Paris 6, Paris, France
Laboratory of Hematology, CHU de Fort de France, Fort de France, France
INSERM, E210, Universite Rene Descartes-Paris 5, Paris, France

* Corresponding author; email: christine.bellanne-chantelot@psl.aphp.fr.

The JAK2V617F mutation does not elucidate the phenotypic variability observed in myeloproliferative neoplasm (MPN) families. A putative tumor suppressor gene, TET2, was recently implicated in MPN and myelodysplastic syndromes through the identification of acquired mutations affecting hematopoietic stem cells. The present study analyzed the TET2 gene in 61 MPN cases from 42 families. Fifteen distinct mutations were identified in 12 (20%) JAK2V617F positive or negative patients. In a patient with two TET2 mutations, the analysis of five blood samples at different phases of her disease showed the sequential occurrence of JAK2V617F and TET2 mutations concomitantly to the disease evolution. Analysis of familial segregation confirmed that TET2 mutations were not inherited but somatically acquired. TET2 mutations were mainly observed (10/12) in patients with primary myelofibrosis (PMF) or patients with polycythemia vera (PV) or essential thrombocythemia (ET) who secondarily evolved towards myelofibrosis or acute myeloid leukemia.

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