Abstract
DDX41 is one of the most frequently altered genes in familial acute myeloid leukemia/myelodysplastic syndrome (AML/MDS). Mutation of DDX41 has been widely reported in various types of myeloid neoplasms. This systematic review and meta-analysis were conducted to assess the clinical characteristics and relationship between DDX41 mutations and OS in myeloid neoplasm patients. We thoroughly searched the PubMed, the Cochrane Library, Embase, Web of Science, MEDLINE, and Google Scholar databases. Two reviewers separately reviewed and extracted the data. Twenty studies totaling 9,058 patients have been integrated into the meta-analysis. The extensive pooled analysis showed a significant association between DDX41 mutations and improved OS (HR 0.70, 95% CI 0.52-0.93, P = 0.01). Subgroup analysis confirmed that DDX41 mutation operated to be a reliable positive indicator of OS when subdivided by different types of myeloid neoplasms. In terms of the clinicopathological value, DDX41 mutations were significantly correlated with the male sex. Age, AML prevalence, bone marrow, or white blood cell counts did not correlate with any findings. The top three genetic variants were p.M1I, p.D140fs, and p.R525H. Co-mutations in patients with DDX41 mutations most commonly include the following: additional sex combs-like 1 (ASXL1), DNA methyltransferase 3 A (DNMT3A), tumor protein p53 (TP53), ten-eleven translocation 2 (TET2) and serine/arginine-rich splicing factor 2 (SRSF2). Our results substantiate that DDX41 mutations were associated with significantly good OS and provide more insight into the clinicopathological characteristics of DDX41 mutations in individuals with myeloid neoplasms.