{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:33:56Z","timestamp":1790696036939,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T00:00:00Z","timestamp":1557187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Myeloid neoplasms with germline <jats:italic>DDX41<\/jats:italic> mutations have been incorporated into the 2017 WHO classification. Limited studies describing the clinicopathologic features and mutation profile are available. We searched for myeloid neoplasms with a <jats:italic>DDX41<\/jats:italic> gene mutation tested by an 81\u2010gene next\u2010generation sequencing panel over a 7\u2010month period. We identified 34 patients with myeloid neoplasms with <jats:italic>DDX41<\/jats:italic> abnormalities; 26 (76%) men and 8 women (24%) [median age, 70\u2009years], 20 acute myeloid leukemia (AML), 10 myelodysplastic syndrome (MDS), 1 chronic myelomonocytic leukemia (CMML) and 3 myeloproliferative neoplasms (MPN). Fifty\u2010nine <jats:italic>DDX41<\/jats:italic> variants were detected: 27 (46%) appeared somatic and 32 (54%) were presumably germline mutations. The majority of presumed germline mutations were upstream of the Helicase 2 domain (93%) and involved loss of the start codon (30%). The majority of somatic mutations were within the Helicase 2 domain (78%), with the missense mutation p.R525H being most common (67%). There was a significant difference in the location of germline or somatic mutations (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.0001). Concomitant mutations were detected involving 19 genes, but only <jats:italic>TP53<\/jats:italic> (n = 11, 32%), <jats:italic>ASXL1<\/jats:italic> (n = 8, 24%), and <jats:italic>JAK2<\/jats:italic> (n = 4, 12%) were recurrent. Twenty (59%) patients showed diploid cytogenetics. Twenty\u2010three (68%) patients presented with AML or MDS\u2010EB\u20102, suggesting an association with high\u2010grade myeloid neoplasm. Patients with myeloid neoplasms carrying <jats:italic>DDX41<\/jats:italic> mutations show male predominance (3:1), higher age at presentation, association with <jats:italic>TP53<\/jats:italic> mutations, and association with high\u2010grade myeloid neoplasms in our cohort at a referral cancer center setting. These findings support the recognition of myeloid neoplasms with <jats:italic>DDX41<\/jats:italic> mutation as unique, need for germline confirmation, and further assessment of family members.<\/jats:p>","DOI":"10.1002\/ajh.25486","type":"journal-article","created":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T04:47:01Z","timestamp":1554785221000},"page":"757-766","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":111,"title":["<i>DDX41<\/i> mutations in myeloid neoplasms are associated with male gender, <i>TP53<\/i> mutations and high\u2010risk disease"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5304-7828","authenticated-orcid":false,"given":"Andr\u00e9s E.","family":"Quesada","sequence":"first","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Routbort","sequence":"additional","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-0390","authenticated-orcid":false,"given":"Courtney D.","family":"DiNardo","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos E.","family":"Bueso\u2010Ramos","sequence":"additional","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7829-5249","authenticated-orcid":false,"given":"Rashmi","family":"Kanagal\u2010Shamanna","sequence":"additional","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2621-3584","authenticated-orcid":false,"given":"Joseph D.","family":"Khoury","sequence":"additional","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5140-3633","authenticated-orcid":false,"given":"Beenu","family":"Thakral","sequence":"additional","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6630-4128","authenticated-orcid":false,"given":"C. 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