{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T12:55:34Z","timestamp":1771332934647,"version":"3.50.1"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Inherited <jats:italic>DDX41<\/jats:italic> mutations cause familial predisposition to hematologic malignancies including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), with the majority of DDX41 mutated MDS\/AMLs described to date harboring germline <jats:italic>DDX41<\/jats:italic> and co-occurring somatic <jats:italic>DDX41<\/jats:italic> variants. DDX41-AMLs were shown to share distinguishing clinical features such as a late AML onset and an indolent disease associated with a favorable outcome. However, genotype-phenotype correlation in DDX41-MDS\/AMLs remain poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we studied the genetic profile, bone marrow morphology and immunophenotype of 51 patients with DDX41 mutations. We further assessed the functional impact of ten previously uncharacterized <jats:italic>DDX41<\/jats:italic> variants of uncertain significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results demonstrate that MDS\/AML cases harboring two <jats:italic>DDX41<\/jats:italic> variants share specific clinicopathologic hallmarks that are not seen in other patients with monoallelic <jats:italic>DDX41<\/jats:italic> related hematologic malignancies. We further showed that the features seen in these individuals with two <jats:italic>DDX41<\/jats:italic> variants were concordant with biallelic <jats:italic>DDX41<\/jats:italic> disruption.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Here, we expand on previous clinicopathologic findings on <jats:italic>DDX41<\/jats:italic> mutated hematologic malignancies. Functional analyses conducted in this study unraveled previously uncharacterized <jats:italic>DDX41<\/jats:italic> alleles and further illustrate the implication of biallelic disruption in the pathophysiology of this distinct AML entity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2023.1153082","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T09:01:51Z","timestamp":1687770111000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Biallelic disruption of DDX41 activity is associated with distinct genomic and immunophenotypic hallmarks in acute 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