Molecular landscape and clinical outcome of <i>SRSF2</i> / <i>TET2</i> Co-mutated myeloid neoplasms

The mutations in <i>SRSF2</i> and <i>TET2</i> genes are frequently present in various myeloid neoplasms. The potential impact of <i>SRSF2</i>/<i>TET2</i> co-mutations on patient survival is incompletely understood. We identified 412 patients with <i>SRSF2</i>/<i>TET2</i> co-mutations from our NextGen sequencing database of around 8000 patients and reported likely the largest cohort study. Our study demonstrated the presence of these co-mutations in a spectrum of myeloid neoplasms, which show different genetic and molecular characteristics. Most of the patients with these co-mutations had normal karyotype. Interestingly, our study provided insights into the prevalence of additional mutations such as <i>ASXL1</i>, <i>RUNX1</i>, and <i>KRAS</i> with this co-mutation and their potential impact on patients' prognosis. We found that <i>ASXL1</i>, <i>RUNX1</i>, and <i>KRAS</i> can negatively impact these patients' survival with different impacts in different morphological diagnosis categories, suggesting a complex interaction between these genes. This study underscores the need for personalized approaches in the treatment of myeloid neoplasms.