[Genetic aberrations and new treatment strategies for pediatric acute myeloid leukemia]

Rinsho Ketsueki. 2018;59(10):2260-2267. doi: 10.11406/rinketsu.59.2260.
[Article in Japanese]

Abstract

The pathogenesis of acute myeloid leukemia (AML) is heterogeneous and caused by various chromosomal aberrations, gene mutations or epigenetic modifications, and deregulated or overregulated gene expression, leading to increased proliferation and decreased hematopoietic progenitor cell differentiation. Although most of these aberrations are correlated with prognosis, accurate risk stratification remains challenging even after incorporating these molecular markers. The development of analytical techniques using microarrays and massive parallel sequencing has identified some gene mutations in adult AML, including DNMT3A and TET2 mutations. However, these mutations are rare in pediatric AML cases. However, a considerable amount of gene fusions was detected in pediatric AML, indicating that a different pathogenesis may exist between adult and pediatric AML. To facilitate genome-based treatment, we should revise the risk classification of AML more appropriately, adopting mutations of NPM1, biallelic CEBPA, and KMT2A-PTD and novel gene fusions, including CBFA2T3-GLIS2 and NUP98-JARID1A. Furthermore, new promising molecular-targeted drugs without side effects are recommended to improve the prognosis of AML.

Keywords: Genetic aberrations; Molecular targets; Pediatric AML; Risk stratification.

Publication types

  • Review

MeSH terms

  • Child
  • Chromosome Aberrations
  • Gene Expression Profiling
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / therapy*
  • Mutation
  • Nucleophosmin
  • Prognosis