Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia

Sci Rep. 2020 Jul 22;10(1):12152. doi: 10.1038/s41598-020-69194-6.

Abstract

The mutational spectrum and prognostic factors of NRAS-mutated (NRASmut) acute myeloid leukemia (AML) are largely unknown. We performed next-generation sequencing (NGS) in 1,149 cases of de novo AML and discovered 152 NRASmut AML (13%). Of the 152 NRASmut AML, 89% had at least one companion mutated gene. DNA methylation-related genes confer up to 62% incidence. TET2 had the highest mutation frequency (51%), followed by ASXL1 (17%), NPM1 (14%), CEBPA (13%), DNMT3A (13%), FLT3-ITD (11%), KIT (11%), IDH2 (9%), RUNX1 (8%), U2AF1 (7%) and SF3B1(5%). Multivariate analysis suggested that age ≥ 60 years and mutations in U2AF1 were independent factors related to failure to achieve complete remission after induction therapy. Age ≥ 60 years, non-M3 types and U2AF1 mutations were independent prognostic factors for poor overall survival. Age ≥ 60 years, non-M3 types and higher risk group were independent prognostic factors for poor event-free survival (EFS) while allogenic hematopoietic stem cell transplantation was an independent prognostic factor for good EFS. Our study provided new insights into the mutational spectrum and prognostic factors of NRASmut AML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • DNA-Binding Proteins / genetics
  • Dioxygenases
  • Disease-Free Survival
  • Female
  • GTP Phosphohydrolases / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • Nucleophosmin
  • Odds Ratio
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Repressor Proteins / genetics
  • Risk Factors
  • Splicing Factor U2AF / genetics
  • Young Adult

Substances

  • ASXL1 protein, human
  • DNA-Binding Proteins
  • Membrane Proteins
  • NPM1 protein, human
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Splicing Factor U2AF
  • U2AF1 protein, human
  • Nucleophosmin
  • Dioxygenases
  • TET2 protein, human
  • GTP Phosphohydrolases
  • NRAS protein, human