Genomics in acute lymphoblastic leukaemia: insights and treatment implications

Nat Rev Clin Oncol. 2015 Jun;12(6):344-57. doi: 10.1038/nrclinonc.2015.38. Epub 2015 Mar 17.


Acute lymphoblastic leukaemia (ALL) is the commonest childhood cancer and an important cause of morbidity from haematological malignancies in adults. In the past several years, we have witnessed major advances in the understanding of the genetic basis of ALL. Genome-wide profiling studies, including microarray analysis and genome sequencing, have helped identify multiple key cellular pathways that are frequently mutated in ALL such as lymphoid development, tumour suppression, cytokine receptors, kinase and Ras signalling, and chromatin remodeling. These studies have characterized new subtypes of ALL, notably Philadelphia chromosome-like ALL, which is a high-risk subtype characterized by a diverse range of alterations that activate cytokine receptors or tyrosine kinases amenable to inhibition with approved tyrosine kinase inhibitors. Genomic profiling has also enabled the identification of inherited genetic variants of ALL that influence the risk of leukaemia development, and characterization of the relationship between genetic variants, clonal heterogeneity and the risk of relapse. Many of these findings are of direct clinical relevance and ongoing studies implementing clinical sequencing in leukaemia diagnosis and management have great potential to improve the outcome of patients with high-risk ALL.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 21 / genetics
  • DNA, Neoplasm / analysis
  • Diploidy
  • Epigenesis, Genetic / genetics
  • Gene Amplification / genetics
  • Gene Expression Profiling / methods
  • Gene Rearrangement / genetics
  • Genes, Neoplasm / genetics
  • Genetic Variation / genetics
  • Genomics*
  • Humans
  • Infant
  • Janus Kinases / genetics
  • Mutation / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Receptors, Cytokine / genetics
  • Recurrence
  • Sequence Analysis, DNA / methods
  • Trans-Activators / genetics
  • Transcriptional Regulator ERG
  • Young Adult


  • CRLF2 protein, human
  • DNA, Neoplasm
  • ERG protein, human
  • Receptors, Cytokine
  • Trans-Activators
  • Transcriptional Regulator ERG
  • Janus Kinases