{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T21:00:14Z","timestamp":1782421214205,"version":"3.54.5"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"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:p><jats:italic>DNMT3A<\/jats:italic> mutations play a prominent role in clonal hematopoiesis and myeloid neoplasms with arginine (R)882 as a hotspot, however the clinical implications of R882 vs. non-R882 mutations in myeloid neoplasms like myelodysplastic syndrome (MDS) is unclear. By data mining with publicly accessible cancer genomics databases and a clinical genomic database from a tertiary medical institution, <jats:italic>DNMT3A<\/jats:italic> R882 mutations were found to be enriched in AML (53% of all DNMT3A mutations) but decreased in frequency in clonal hematopoiesis of indeterminate potential (CHIP) (10.6%) or other myeloid neoplasms including MDS (27%) (p&amp;lt;.001). Next with the largest cohort of patients with <jats:italic>DNMT3A<\/jats:italic> R882 mutant MDS known to date from multiple institutions, <jats:italic>DNMT3A<\/jats:italic> R882 mutant MDS cases were shown to have more severe leukopenia, enriched <jats:italic>SRSF2<\/jats:italic> and <jats:italic>IDH2<\/jats:italic> mutations, increased cases with excess blasts (47% vs 22.5%, p=.004), markedly increased risk of AML transformation (25.8%, vs. 1.7%, p=.0001) and a worse progression-free survival (PFS) (median 20.3, vs. &amp;gt;50 months, p=.009) than non-R882 mutant MDS cases. <jats:italic>DNMT3A R882<\/jats:italic> mutation is an independent risk factor for worse PFS, and importantly the differences in the risk of AML transformation between R882 vs. non-R882 mutant patients cannot be explained by different treatment approaches. Interestingly the higher risk of AML transformation and the worse PFS in <jats:italic>DNMT3A<\/jats:italic> R882 mutant MDS cases are mitigated by coexisting <jats:italic>SF3B1<\/jats:italic> or <jats:italic>SRSF2<\/jats:italic> mutations. The unique clinicopathologic features of <jats:italic>DNMT3A<\/jats:italic> R882 mutant MDS shed light on the prognostic and therapeutic implications of <jats:italic>DNMT3A<\/jats:italic> R882 mutations.<\/jats:p>","DOI":"10.3389\/fonc.2022.849376","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T05:06:41Z","timestamp":1646024801000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["DNMT3A R882 Mutations Confer Unique Clinicopathologic Features in MDS Including a High Risk of AML 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