An inherited gain-of-function risk allele in EPOR predisposes to familial JAK2 myeloproliferative neoplasms.
Fiche publication
Date publication
mars 2022
Journal
British journal of haematology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DECONINCK Eric
Tous les auteurs :
Moraes GR, Pasquier F, Marzac C, Deconinck E, Damanti CC, Leroy G, El-Khoury M, El Nemer W, Kiladjian JJ, Raslova H, Najman A, Vainchenker W, Marty C, Bellanné-Chantelot C, Plo I
Lien Pubmed
Résumé
Myeloproliferative neoplasms (MPN) are mainly sporadic but inherited variants have been associated with higher risk development. Here, we identified an EPOR variant (EPOR ) in a large family diagnosed with JAK2 -positive polycythaemia vera (PV) or essential thrombocytosis (ET). We investigated its functional impact on JAK2 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 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.
Mots clés
EPOR P488S , JAK2 V617F , familial myeloproliferative neoplasms, germline factor, predisposition
Référence
Br J Haematol. 2022 Mar 30;: