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

Abstract

<b><i>Introduction:</i></b> This study aimed to identify genetic predictors of treatment response and survival in patients with myeloid neoplasms treated with hypomethylating agents (HMAs). <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> A single gene with the most common mutations was <i>TP53</i> (14 of 59 patients), and mutations in RAS pathway-related genes including <i>KRAS</i>, <i>NRAS</i>, <i>FLT3</i>, <i>PTPN11</i>, <i>CBL</i>, and <i>KIT</i> 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 &#x3e;75 years (<i>p</i> = 0.007), 3 or more gene mutations (<i>p</i> = 0.004), mutations in RAS pathway-related genes (<i>p</i> = 0.033), and a mutated <i>NRAS</i> gene (<i>p</i> = 0.042). An age &#x3e;75 years (hazard ratio 2.946), diagnosis of AML (hazard ratio 2.915), and mutations in <i>NRAS</i> (hazard ratio 4.440) were identified as poor prognostic factors for survival. <b><i>Conclusion:</i></b> In conclusion, mutations in RAS pathway-related genes were predictors of a poor response to HMAs. Particularly, mutated <i>NRAS</i> was associated with inferior survival rates.