Does SF3B1/TET2 double mutation portend better or worse prognosis than isolated SF3B1 or TET2 mutation?

Abstract

Background: Mutations in splicing factor 3b subunit 1 (SF3B1) have been reported to be associated with a favorable prognosis, while the prognostic impact of tet methylcytosine dioxygenase 2 (TET2) mutations is still controversial. The clinical significance of combined SF3B1 and TET2 mutation is even more uncertain. In this study, the clinical consequences of concurrent double SF3B1/TET2 mutation were compared with isolated SF3B1 or TET2 mutation. Materials and Methods: The demographics, diagnosis, cytogenetic abnormalities, and overall survival time of 130 patients with isolated SF3B1 (n=48) or TET2 mutation (n=54), or double SF3B1/TET2 mutation (n=28) were compared by next-generation sequencing. Results: Patients with double mutation were found to be significantly older than patients with isolated TET2 mutation. Patients with double mutation or isolated SF3B1 mutation were less likely to be diagnosed with acute myeloid leukemia than patients with isolated TET2 mutation. Patients with myelodysplasia had a higher percentage of double or isolated SF3B1 mutation, while patients with myeloproliferative neoplasms had a higher percentage of isolated TET2 mutation. Patients with double mutation more frequently had increased ring sideroblasts similarly to patients with isolated SF3B1 mutation. The percentage of patients with normal cytogenetics or good cytogenetic abnormalities was significantly higher in patients with double mutation than those with isolated mutation. Finally, in patients with myelodysplasia and normal cytogenetics, the median survival time in those with double mutation was significantly longer than in those with isolated SF3B1 mutation, even though the overall survival curve was not statistically significant. Conclusion: TET2 mutation appeared not to have additional effects when combined with SF3B1, and patients with double mutation appeared to have at least as, good as or even better prognosis than patients with isolated mutation.