{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:29:51Z","timestamp":1793644191621,"version":"4.5.1"},"reference-count":37,"publisher":"American Society of Hematology","issue":"7","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,8,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Germline DDX41 variants are the most common mutations predisposing to acute myeloid leukemia (AML)\/myelodysplastic syndrome (MDS) in adults, but the causal variant (CV) landscape and clinical spectrum of hematologic malignancies (HMs) remain unexplored. Here, we analyzed the genomic profiles of 176 patients with HM carrying 82 distinct presumably germline DDX41 variants among a group of 9821 unrelated patients. Using our proposed DDX41-specific variant classification, we identified features distinguishing 116 patients with HM with CV from 60 patients with HM with variant of uncertain significance (VUS): an older age (median 69 years), male predominance (74% in CV vs 60% in VUS, P = .03), frequent concurrent somatic DDX41 variants (79% in CV vs 5% in VUS, P &amp;lt; .0001), a lower somatic mutation burden (1.4 \u00b1 0.1 in CV vs 2.9 \u00b1 0.04 in VUS, P = .012), near exclusion of canonical recurrent genetic abnormalities including mutations in NPM1, CEBPA, and FLT3 in AML, and favorable overall survival (OS) in patients with AML\/MDS. This superior OS was determined independent of blast count, abnormal karyotypes, and concurrent variants, including TP53 in patients with AML\/MDS, regardless of patient\u2019s sex, age, or specific germline CV, suggesting that germline DDX41 variants define a distinct clinical entity. Furthermore, unrelated patients with myeloproliferative neoplasm and B-cell lymphoma were linked by DDX41 CV, thus expanding the known disease spectrum. This study outlines the CV landscape, expands the phenotypic spectrum in unrelated DDX41-mutated patients, and underscores the urgent need for gene-specific diagnostic and clinical management guidelines.<\/jats:p>","DOI":"10.1182\/blood.2021015135","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T14:52:22Z","timestamp":1654613542000},"page":"716-755","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":91,"title":["The genetic landscape of germline\n                    <i>DDX41<\/i>\n                    variants predisposing to myeloid neoplasms"],"prefix":"10.1182","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4711-362X","authenticated-orcid":false,"given":"Peng","family":"Li","sequence":"first","affiliation":[{"name":"1Division of Hematopathology, Department of Pathology, University of Utah Health, Salt Lake City, UT;"},{"name":"2Genomics Laboratory, ARUP Laboratories, Salt Lake City, UT;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0081-7876","authenticated-orcid":false,"given":"Sara","family":"Brown","sequence":"additional","affiliation":[{"name":"2Genomics Laboratory, ARUP Laboratories, Salt Lake City, UT;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Williams","sequence":"additional","affiliation":[{"name":"1Division of Hematopathology, Department of Pathology, University of Utah Health, Salt Lake City, UT;"},{"name":"2Genomics Laboratory, ARUP Laboratories, Salt Lake City, UT;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"White","sequence":"additional","affiliation":[{"name":"2Genomics Laboratory, ARUP Laboratories, Salt Lake City, UT;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1815-7666","authenticated-orcid":false,"given":"Wei","family":"Xie","sequence":"additional","affiliation":[{"name":"3Department of Pathology, School of Medicine, Oregon Health and Science University, Portland, OR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8177-0538","authenticated-orcid":false,"given":"Wei","family":"Cui","sequence":"additional","affiliation":[{"name":"4Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Peker","sequence":"additional","affiliation":[{"name":"5Division of Hematopathology, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Lei","sequence":"additional","affiliation":[{"name":"6Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA;"},{"name":"7Department of Pathology, Stanford University, School of Medicine, Stanford, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian A.","family":"Kunder","sequence":"additional","affiliation":[{"name":"7Department of Pathology, Stanford University, School of Medicine, Stanford, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan-You","family":"Wang","sequence":"additional","affiliation":[{"name":"8Department of Pathology & Immunology, University of California San Diego Health System, La Jolla, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah S.","family":"Murray","sequence":"additional","affiliation":[{"name":"8Department of Pathology & Immunology, University of California San Diego Health System, La Jolla, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennie","family":"Vagher","sequence":"additional","affiliation":[{"name":"9Department of Internal Medicine, University of Utah Health, Salt Lake City, UT; and"},{"name":"10Huntsman Cancer Institute, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibor","family":"Kovacsovics","sequence":"additional","affiliation":[{"name":"9Department of Internal Medicine, University of Utah Health, Salt Lake City, UT; and"},{"name":"10Huntsman Cancer Institute, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay L.","family":"Patel","sequence":"additional","affiliation":[{"name":"1Division of Hematopathology, Department of Pathology, University of Utah Health, Salt Lake City, UT;"},{"name":"2Genomics Laboratory, ARUP Laboratories, Salt Lake City, 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