Impact of mutations in FLT3, PTPN11 and RAS genes on the overall survival of pediatric B cell precursor acute lymphoblastic leukemia in Brazil

Leuk Lymphoma. 2014 Jul;55(7):1501-9. doi: 10.3109/10428194.2013.847934. Epub 2014 Feb 6.

Abstract

We analyzed mutations in four genes (FLT3, KRAS/NRAS and PTPN11) that might disrupt the RAS/mitogen activated protein kinase (MAPKinase) signaling pathway, to evaluate their prognostic value in children younger than 16 years old with B-cell precursor acute lymphoblastic leukemia (Bcp-ALL). The overall survival (OS) was determined with the Kaplan-Meier method. MAPKinase genes were mutated in 25.4% and 20.1% of childhood and infant Bcp-ALL, respectively. Children with hyperdiploidy were more prone to harboring a MAPKinase gene mutation (odds ratio [OR] 3.18; 95% confidence interval [CI] 1.07-9.49). The mean OS of all cases was 54.0 months. FLT3 and PTPN11 mutations had no impact on OS. K/NRAS mutations were strongly associated with MLL-AFF1 (OR 5.78; 95% CI 1.00-33.24), and conferred poorer OS (p = 0.034) in univariate analysis.

Keywords: Acute lymphoblastic leukemia; FLT3; K/NRAS; PTPN11; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brazil
  • Child
  • Child, Preschool
  • Female
  • Genes, ras*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation*
  • Odds Ratio
  • Oncogene Proteins, Fusion / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / mortality*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Prognosis
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics*
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

  • Oncogene Proteins, Fusion
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11