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Updated: Apr 5, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies
Joseph Saliba1,2,3,4, Cécile Saint-Martin1,2,3,5, Antonio Di Stefano1,2,3,4
1INSERM, Unité Mixte de Recherche (UMR) 1170, Villejuif, France.
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.
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