TP53 mutations and relevance of expression of TP53 pathway genes in paediatric acute myeloid leukaemia

Br J Haematol. 2020 Mar;188(5):736-739. doi: 10.1111/bjh.16229. Epub 2019 Oct 6.

Abstract

Limited data are available on the incidence and impact of TP53 alterations and TP53 pathway deregulation in paediatric acute myeloid leukaemia (AML). We analysed TP53 alterations in bone marrow samples of 229 patients with de novo paediatric AML, and detected heterozygous missense exon mutations in two patients (1%) and 17p deletions of the TP53 gene in four patients (2%). These patients more frequently had complex karyotype (50% vs. 4%, P = 0·002) or adverse cytogenetic abnormalities, including complex karyotype (67% vs. 17%, P = 0·013), compared to TP53 wild-type. Differential expression of TP53 pathway genes was associated with poor survival, indicating a role for TP53 regulators and effector genes.

Keywords: RRM2B; TP53; acute myeloid leukaemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 17 / metabolism
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Infant
  • Infant, Newborn
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / metabolism
  • Leukemia, Myeloid, Acute* / mortality
  • Male
  • Mutation*
  • Signal Transduction*
  • Smith-Magenis Syndrome* / genetics
  • Smith-Magenis Syndrome* / metabolism
  • Smith-Magenis Syndrome* / mortality
  • Survival Rate
  • Tumor Suppressor Protein p53* / biosynthesis
  • Tumor Suppressor Protein p53* / genetics

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53

Supplementary concepts

  • Chromosome 17 deletion