{"doi":"10.1111/bjh.18165","title":"An inherited gain‐of‐function risk allele in <scp><i>EPOR</i></scp> predisposes to familial <scp><i>JAK2</i><sup>V617F</sup></scp> myeloproliferative neoplasms","abstract":"<jats:title>Summary</jats:title><jats:p>Myeloproliferative neoplasms (MPN) are mainly sporadic but inherited variants have been associated with higher risk development. Here, we identified an <jats:italic>EPOR</jats:italic> variant (<jats:italic>EPOR</jats:italic><jats:sup>P488S</jats:sup>) in a large family diagnosed with <jats:italic>JAK2</jats:italic><jats:sup>V617F</jats:sup>‐positive polycythaemia vera (PV) or essential thrombocytosis (ET). We investigated its functional impact on <jats:italic>JAK2</jats:italic><jats:sup>V617F</jats:sup> 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<jats:sup>P488S</jats:sup> 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.</jats:p>","journal":"British Journal of Haematology","year":2022,"id":601383,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":233802,"name":"Florence Pasquier","orcid":"0000-0001-9880-9788","position":1,"is_corresponding":false},{"id":663669,"name":"Christophe Marzac","orcid":"0000-0001-5065-0376","position":2,"is_corresponding":false},{"id":1542025,"name":"Eric Deconinck","orcid":"0000-0002-6006-8088","position":3,"is_corresponding":false},{"id":1542026,"name":"Carlotta Caterina Damanti","orcid":null,"position":4,"is_corresponding":false},{"id":1542027,"name":"Gwendoline Leroy","orcid":null,"position":5,"is_corresponding":false},{"id":1542028,"name":"Mira El‐Khoury","orcid":null,"position":6,"is_corresponding":false},{"id":317750,"name":"Wassim El Nemer","orcid":"0000-0001-8184-427X","position":7,"is_corresponding":false},{"id":438286,"name":"Jean‐Jacques Kiladjian","orcid":"0000-0002-8121-438X","position":8,"is_corresponding":false},{"id":1542030,"name":"Hana Raslova","orcid":null,"position":9,"is_corresponding":false},{"id":1542031,"name":"Albert Najman","orcid":null,"position":10,"is_corresponding":false},{"id":663677,"name":"William Vainchenker","orcid":"0000-0003-4705-202X","position":11,"is_corresponding":false},{"id":663670,"name":"Caroline Marty","orcid":"0000-0003-4350-2302","position":12,"is_corresponding":false},{"id":251702,"name":"Christine Bellanné‐Chantelot","orcid":"0000-0001-8415-6771","position":13,"is_corresponding":false},{"id":663679,"name":"Isabelle Plo","orcid":"0000-0002-5915-6910","position":14,"is_corresponding":false},{"id":1542024,"name":"Graciela Rabadan Moraes","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"An inherited gain‐of‐function risk allele in <scp><i>EPOR</i></scp> predisposes to familial <scp><i>JAK2</i><sup>V617F</sup></scp> myeloproliferative neoplasms","abstract":"<jats:title>Summary</jats:title><jats:p>Myeloproliferative neoplasms (MPN) are mainly sporadic but inherited variants have been associated with higher risk development. Here, we identified an <jats:italic>EPOR</jats:italic> variant (<jats:italic>EPOR</jats:italic><jats:sup>P488S</jats:sup>) in a large family diagnosed with <jats:italic>JAK2</jats:italic><jats:sup>V617F</jats:sup>‐positive polycythaemia vera (PV) or essential thrombocytosis (ET). We investigated its functional impact on <jats:italic>JAK2</jats:italic><jats:sup>V617F</jats:sup> 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<jats:sup>P488S</jats:sup> 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.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35355248","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"Association pour la Recherche sur le Cancer","grant_id":"","title":null},{"funder_name":"Fondation Maladies Rares","grant_id":"","title":null},{"funder_name":"Institut National Du Cancer","grant_id":"","title":null}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"hybrid","license":"cc-by-nc","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjh.18165","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjh.18165","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1111/bjh.18165","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Humans","Myeloproliferative Disorders","Polycythemia Vera","Receptors, Erythropoietin","Mutation","Alleles","Janus Kinase 2","Thrombocythemia, Essential","Gain of Function Mutation"],"keywords":["Predisposition","Jak2 V617f","Familial Myeloproliferative Neoplasms","Germline Factor","Epor P488s"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T16:10:25.975705Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}