DDX41 mutations in myeloid neoplasms are associated with male gender, TP53 mutations and high‐risk disease

Myeloid neoplasms with germline DDX41 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 DDX41 gene mutation tested by an 81‐gene next‐generation sequencing panel over a 7‐month period. We identified 34 patients with myeloid neoplasms with DDX41 abnormalities; 26 (76%) men and 8 women (24%) [median age, 70 years], 20 acute myeloid leukemia (AML), 10 myelodysplastic syndrome (MDS), 1 chronic myelomonocytic leukemia (CMML) and 3 myeloproliferative neoplasms (MPN). Fifty‐nine DDX41 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 (P