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

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

Sarah K Tasian  1   2 , Stephen P Hunger  1   2
Affiliations
Review

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

Sarah K Tasian et al. Br J Haematol. 2017 Mar.

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.

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Figures

Figure 1
Figure 1. Improved overall survival of children with ALL treated on cooperative group trials in North America
Parenthetical numbers indicate number of subjects analysed for each treatment era. Longer-term follow-up is available for some populations (not shown). Data provided by the Children’s Oncology Group.
Figure 2
Figure 2. Recurrent genomic alterations in childhood ALL
Relative incidence of major translocations and other alterations are delineated for (A) B cell acute lymphoblastic leukaemia (B-ALL) and (B) T cell acute lymphoblastic leukaemia (T-ALL).
See this image and copyright information in PMC

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