Clinical significance of recurrent copy number aberrations in B-lineage acute lymphoblastic leukaemia without recurrent fusion genes across age cohorts

Br J Haematol. 2017 Aug;178(4):583-587. doi: 10.1111/bjh.14721. Epub 2017 Apr 25.

Abstract

Copy number aberrations (CNAs) represent cooperating events in B-lineage acute lymphoblastic leukaemia (B-ALL); however, their clinical relevance across different age cohorts is unclear. We analysed the recurrent CNAs in 157 age-stratified B-ALL negative cases for recurrent rearrangements (B-NEG ALL), and their association with patients' clinico-biological features. We found that: (i) CDKN2A/RB1-deleted and EBF1-deleted adults had a shorter disease-free survival than those with wild-type, (ii) among the unfavourable markers, CDKN2A/RB1 deletions and K/NRAS mutations retained their impact in multivariate analysis, encouraging the evaluation of CDKN2A/RB1 deletions and RAS mutations in the diagnostic/prognostic workflow to refine ALL risk assessment.

Keywords: CDKN2A; K/NRAS; acute lymphoblastic leukaemia; copy number aberrations (CNAs); prognostic markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Child
  • DNA Copy Number Variations / genetics*
  • DNA, Neoplasm / genetics
  • Female
  • GTP Phosphohydrolases / genetics
  • Gene Deletion
  • Genes, p16
  • Genetic Markers / genetics
  • Humans
  • Infant
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Mutation
  • Neoplasm Proteins / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Prognosis
  • Retinoblastoma Binding Proteins / genetics
  • Survival Analysis
  • Ubiquitin-Protein Ligases / genetics
  • Young Adult

Substances

  • DNA, Neoplasm
  • Genetic Markers
  • Membrane Proteins
  • Neoplasm Proteins
  • RB1 protein, human
  • Retinoblastoma Binding Proteins
  • Ubiquitin-Protein Ligases
  • GTP Phosphohydrolases
  • NRAS protein, human