Genomic characterization of paediatric acute lymphoblastic leukaemia: an opportunity for precision medicine therapeutics

Br J Haematol. 2017 Mar;176(6):867-882. doi: 10.1111/bjh.14474. Epub 2016 Dec 16.

Abstract

Major advances in genetic and epigenetic profiling of acute lymphoblastic leukaemia (ALL) have enhanced the understanding of key biological subsets of de novo and relapsed ALL, which has led to improved risk stratification of patients. These achievements have further defined critical leukaemia-associated pathways and somatic alterations that may be preferentially sensitive to treatment with kinase inhibitors, epigenetic therapy or other novel agents. Therapeutic success in childhood ALL currently relies upon refined risk stratification of patients based on (i) underlying biological and clinical characteristics, and (ii) depth of initial treatment response with appropriate modulation of chemotherapy intensity. This review describes the current mutational landscape of childhood ALL and discusses opportunities for substantial improvements in survival with implementation of molecularly targeted therapies.

Keywords: acute lymphoblastic leukaemia; genomics; paediatrics; precision medicine; therapy.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genetic Variation
  • Genome-Wide Association Study
  • Genomics* / methods
  • Humans
  • Molecular Targeted Therapy*
  • Precision Medicine* / methods
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Recurrence