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An inherited gain‐of‐function risk allele in EPOR predisposes to familial JAK2 V617F myeloproliferative neoplasms
Author(s) -
Rabadan Moraes Graciela,
Pasquier Florence,
Marzac Christophe,
Deconinck Eric,
Damanti Carlotta Caterina,
Leroy Gwendoline,
ElKhoury Mira,
El Nemer Wassim,
Kiladjian JeanJacques,
Raslova Hana,
Najman Albert,
Vainchenker William,
Marty Caroline,
BellannéChantelot Christine,
Plo Isabelle
Publication year - 2022
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.18165
Subject(s) - jak2 v617f , polycythaemia , polycythemia vera , allele , stat5 , erythropoietin receptor , haematopoiesis , thrombocytosis , janus kinase 2 , genetics , biology , cancer research , immunology , medicine , phosphorylation , receptor , stem cell , mutation , gene , platelet
Summary Myeloproliferative neoplasms (MPN) are mainly sporadic but inherited variants have been associated with higher risk development. Here, we identified an EPOR variant ( EPOR P488S ) in a large family diagnosed with JAK2 V617F ‐positive polycythaemia vera (PV) or essential thrombocytosis (ET). We investigated its functional impact on JAK2 V617F clonal amplification in patients and found that the variant allele fraction (VAF) was low in PV progenitors but increase strongly in mature cells. Moreover, we observed that EPOR P488S alone induced a constitutive phosphorylation of STAT5 in cell lines or primary cells. Overall, this study points for searching inherited‐risk alleles affecting the JAK2/STAT pathway in MPN.