Institut Gustave Roussy

Centre National De La Recherche Scientifique

Assistance Publique-hopitaux De Paris

Université Paris—sud

Universite Paris Cité

College De France

Inserm

Isabelle Plo

William Vainchenker

Hugues De The

Cécile Saint-Martin

Joseph Saliba

Antonio D Di Stefano

Christine Bellane-Chantelot

Bruno Cassinat

Valérie Lallemand-breitenbach

Jean-Luc Villeval

Antonio Di Stefano

Christine Bellanne-Chantelot

Jean-Jacques Kiladjian

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

Growing community of inventors

Etampes, France

Isabelle Plo