| Literature DB >> 26280900 |
Joseph Saliba1,2,3,4, Cécile Saint-Martin1,2,3,5, Antonio Di Stefano1,2,3,4, Gaëlle Lenglet1,2,3,4, Caroline Marty1,2,3,4, Boris Keren5, Florence Pasquier1,2,3,4, Véronique Della Valle1,2,3, Lise Secardin1,2,3,4, Gwendoline Leroy5, Emna Mahfoudhi1,2,3,4,6, Sarah Grosjean1,2,3,4, Nathalie Droin1,2,3, M'boyba Diop1,2,3, Philippe Dessen1,2,3, Sabine Charrier7, Alberta Palazzo1,2,3, Jane Merlevede1,2,3, Jean-Côme Meniane8, Christine Delaunay-Darivon8, Pascal Fuseau9, Françoise Isnard10,11, Nicole Casadevall1,12, Eric Solary1,2,3, Najet Debili1,2,3, Olivier A Bernard1,2,3, Hana Raslova1,2,3, Albert Najman10,11, William Vainchenker1,2,3,4,13, Christine Bellanné-Chantelot1,2,3,5,11, Isabelle Plo1,2,3,4.
Abstract
No major predisposition gene for familial myeloproliferative neoplasms (MPN) has been identified. Here we demonstrate that the autosomal dominant transmission of a 700-kb duplication in four genetically related families predisposes to myeloid malignancies, including MPN, frequently progressing to leukemia. Using induced pluripotent stem cells and primary cells, we demonstrate that overexpression of ATG2B and GSKIP enhances hematopoietic progenitor differentiation, including of megakaryocytes, by increasing progenitor sensitivity to thrombopoietin (TPO). ATG2B and GSKIP cooperate with acquired JAK2, MPL and CALR mutations during MPN development. Thus, the germline duplication may change the fitness of cells harboring signaling pathway mutations and increases the probability of disease development.Entities:
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Year: 2015 PMID： 26280900 DOI： 10.1038/ng.3380
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330