The Prognostic Ability of RAS Pathway-Related Gene Mutations in Patients with Myeloid Neoplasms Treated with Hypomethylating Agents.

Introduction This study aimed to identify genetic predictors of treatment response and survival in patients with myeloid neoplasms treated with hypomethylating agents (HMAs). Methods We performed next-generation sequencing on bone marrow aspiration samples of 59 patients diagnosed with acute myeloid leukemia (AML), myelodysplastic syndrome with excess blasts-2, or chronic myelomonocytic leukemia and treated with decitabine or azacitidine as a frontline therapy. Results A single gene with the most common mutations was TP53 (14 of 59 patients), and mutations in RAS pathway-related genes including KRAS, NRAS, FLT3, PTPN11, CBL, and KIT were found in 28.8% of patients. The overall response rate to HMAs was 33.9%. Predictive factors for a poor response were an age >75 years (p = 0.007), 3 or more gene mutations (p = 0.004), mutations in RAS pathway-related genes (p = 0.033), and a mutated NRAS gene (p = 0.042). An age >75 years (hazard ratio 2.946), diagnosis of AML (hazard ratio 2.915), and mutations in NRAS (hazard ratio 4.440) were identified as poor prognostic factors for survival. Conclusion In conclusion, mutations in RAS pathway-related genes were predictors of a poor response to HMAs. Particularly, mutated NRAS was associated with inferior survival rates.