Institut Gustave Roussy

Assistance Publique-hopitaux De Paris

Institut National De La Sante Et De La Recherche Medicale

Université Paris—sud

Universite De Versailles-st Quentin En Yvelines

Centre Henri Becquerel

Université Paris Descartes

Université Pierre Et Marie Curie (paris 6)

Université Pierre Et Marie Curie

Aventis Pharma S.a.

Institut National De La Recherche Scientifique

Université Paris-sud 11

Ipsogen

William Vainchenker

Nicole Casadevall

Jean-Pierre Le Couedic

Olivier Bernard

Christian Bastard

Michaela Fontenay

Francois Delhommeau

Franck Viguie

Valerie Ugo

Valérie Ugo

Chloe James

James Chloe

Michel Perricaudet

Yves Beuzard

Olivier Danos

Nadia Naffakh

Philippe Moullier

Jean-Michel Heard

Vincent Descamps

Valeria Ugo

Christine Bellane-Chantelot

Cécile Saint-Martin

Joseph Saliba

Antonio D Di Stefano

Isabelle Plo

Chloé James

James Chloé

Antonio Di Stefano

Christine Bellanne-Chantelot

François Delhommeau

The present inventors identified for the first time a germline genomic alteration that accounts for familial myeloproliferative neoplasms (MPN) and myeloid malignancies. More precisely, they identified a 700 kb germline duplication that proposes patients to essential thrombocythemia (ET) with a high frequency of evolution to myelofibrosis (MF), secondary myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Two out of the 6 duplicated genes (namely ATG2B and GSKIP) have been shown to be overexpressed in hematopoietic progenitors, and this overexpression cooperates with classical mutations in JAK2, MPL, and CALR to generate the MPN phenotype. The presence of the 700 kb germline duplication is thus of poor prognosis for a MPN patient. The present invention discloses a method for detecting a predisposition of developing a MPN, as well as a prognostic method for assessing the probability that an ET-suffering patient will develop a myelofibrosis, a secondary MDS or an AML. It also discloses a treating method for delaying MPN worsening, said treating method involving the inhibition of the ATG2B and GSKIP duplicated genes.

Prognostic marker for myeloproliferative neoplasms

The present invention concerns an in vitro method for diagnosing a myeloid tumour or a lymphoid tumour in a subject, which comprises the step of analyzing a biological sample from said subject by (i) detecting the presence of a mutation in the Ten Eleven Translocation protein family member 2 gene (TET2) coding for the polypeptide having the sequence SEQ ID NO: 2, and/or (ii) analyzing the expression of the TET2 gene; wherein the detection of such a TET2 mutation, of the absence of expression of TET2 or of the expression of a truncated TET2 is indicative of a subject developing or predisposed to develop a myeloid tumour or a lymphoid tumour.

TET2 as a diagnostic and pronostic marker in hematopoietic neoplasms

The present invention concerns the V617F variant of the protein-tyrosine kinase JAK2, said variant being responsible for Vaquez Polyglobulia. The invention also relates to a first intention diagnostic method for erythrocytosis and thrombocytosis allowing their association with myeloproliferative disorders, or to the detection of the JAK2 V617F variant in myeloproliferative disorders allowing their reclassification in a new nosological group.

Identification of a JAK2 mutation in polycythemia vera

TET2 as a diagnostic and prognostic marker in hematopoietic neoplasms

Identification of a JAK2 mutation in Polycythemia Vera

The present invention concerns an in vitro method for diagnosing a myeloid tumor or a lymphoid tumor in a subject, which comprises the step of analyzing a biological sample from said subject by (i) detecting the presence of a mutation in the Ten Eleven Translocation protein family member 2 gene (TET2) coding for the polypeptide having the sequence SEQ ID NO:2, and/or (ii) analyzing the expression of the TET2 gene; wherein the detection of such a TET2 mutation, of the absence of expression of TET2 or of the expression of a truncated TET2 is indicative of a subject developing or predisposed to develop a myeloid tumor or a lymphoid tumor.

TET2 as a new diagnostic and pronostic marker in hematopoietic neoplasms

Identification of a JAK2 mutation involved in vaquez polyglobulia

The present invention provides cell compositions for in vivo implantation, and designed for the sustained and controlled delivery of therapeutic substances.

Composition for the in vivo production of therapeutic products

Growing community of inventors

Paris, France

William Vainchenker