Mutational Spectrum and Clinical Outcomes of Myelodysplastic/Myeloproliferative Neoplasms: A Single-Institution Study in Korea with Emphasis on U2AF1

<b>Background</b>: Myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are rare hematopoietic disorders that exhibit overlapping pathological and molecular features of both MDS and MPN. This study aimed to investigate the mutational profiles and prognostic implications of MDS/MPN subtypes in Korean patients. <b>Methods</b>: We retrospectively reviewed 53 patients with MDS/MPN who underwent bone marrow examination and next-generation sequencing panel testing. Overall survival was analyzed with 3-year censoring. The cohort included chronic myelomonocytic leukemia (CMML; <i>N</i> = 30); MDS/MPN with neutrophilia (<i>N</i> = 6); MDS/MPN with <i>SF3B1</i> mutation and thrombocytosis (<i>N =</i> 4); and MDS/MPN, not otherwise specified (MDS/MPN-NOS; <i>N =</i> 13). <b>Results</b>: The most frequently mutated gene was <i>ASXL1</i> (52.8%), followed by <i>TET2</i> (39.6%) and <i>U2AF1</i> (18.9%), in total MDS/MPN. <i>U2AF1</i> mutations were particularly frequent in myelodysplastic CMML (33.3%) and MDS/MPN-NOS (30.8%). In CMML, <i>ASXL1</i> and <i>TET2</i> mutations were associated with a trend toward better prognosis compared with wild-type (HR 0.21, <i>p</i> = 0.052; HR 0.25, <i>p</i> = 0.057, respectively), while <i>U2AF1</i> mutations were associated with adverse prognosis in univariate analysis with borderline significance (HR 12.20, <i>p</i> = 0.050). Clinical/Molecular CMML-Specific Prognostic Scoring System and Mayo Molecular Model showed stepwise survival patterns across risk groups without statistical significance. In univariate analysis, transfusion dependency was associated with poor prognosis (HR 7.78, <i>p</i> = 0.013). <b>Conclusions</b>: This study provides the first single-institution analysis in Korean patients with MDS/MPN and identified <i>U2AF1</i> mutations as a potentially significant prognostic factor, enhancing the molecular understanding of MDS/MPN.