ArticleLeukemia2026
DDX41-mutant myeloid neoplasms defy current prognostic schemes and require a dedicated risk scoring system: a multicenter, retrospective study.
Article in Leukemia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Allogeneic hematopoietic cell transplantation for myelodysplastic syndrome in young adults: A retrospective study on behalf of the EBMT Chronic Malignancies Working Party.Bone marrow transplantation · 2026Article
- A 2026 update on myelodysplastic neoplasms: current state, challenges and future directions.Nature reviews. Clinical oncology · 2026Review
- MDS/AML-associated DDX41 helicase facilitates homologous recombination repair by potentially resolving R-loops.Nucleic acids research · 2026Article
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Authors and funding
33 authors.
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Abstract
DDX41-mutant myeloid neoplasia (MN) is characterized by unique clinical-molecular characteristics and prognosis. However, it is poorly understood how DDX41 mutational constellations drive MN outcomes. We leveraged collaborative resources to test the new 2022 MN diagnostic and prognostic schemes and account for the diverse mutational configurations of DDX41-mutant MN. Diagnostic re-classification from 2016 to 2022 schemes showed an overall shift of 14.9% and 29.7% for DDX41-mutant MDS and AML, respectively. Current prognostic systems (IPSS-R/M and ELN 2017/22) showed poor applicability to DDX41-mutant MN when compared to wild-type counterparts. Dissecting all possible DDX41 configurations, we assigned the greatest prognostic impact to R525H somatic and germline truncating hits. The former impacted most survival outcomes, while the latter were enriched in AML, independently predicting leukemic evolution. Such features had synergistic effects, albeit with different treatment interactions, and were included in DDX41-specific multivariable outcome models, which alleviated the shortcomings of the current prognostic MN algorithms. We here show that current prognostic tools are not able to adequately assess leukemic evolution and survival outcomes in DDX41-mutant MN. Additional risk factors inherent to this MN subentity hold a prognostic significance beyond the consideration of traditional disease-specific variables, substantiating the need for a dedicated risk scoring system.
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