公开(公告)号：US11732303B2

公开(公告)日：2023-08-22

申请号：US15739454

申请日：2016-06-24

申请人： Institut Gustave-Roussy

发明人： Christine Bellane-Chantelot ,  Isabelle Plo ,  William Vainchenker ,  Cécile Saint-Martin ,  Antonio D Di Stefano ,  Joseph Saliba

IPC分类号： C12Q1/6886 ,  G01N33/574

CPC分类号： C12Q1/6886 ,  G01N33/57426 ,  C12Q2600/156

摘要： 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.