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Review
. 2013 Jun 1;381(9881):1943-55.
doi: 10.1016/S0140-6736(12)62187-4. Epub 2013 Mar 22.

Acute lymphoblastic leukaemia

Hiroto Inaba  1 , Mel Greaves, Charles G Mullighan
Affiliations
Review

Acute lymphoblastic leukaemia

Hiroto Inaba et al. Lancet. .

Abstract

Acute lymphoblastic leukaemia occurs in both children and adults but its incidence peaks between 2 and 5 years of age. Causation is multifactorial and exogenous or endogenous exposures, genetic susceptibility, and chance have roles. Survival in paediatric acute lymphoblastic leukaemia has improved to roughly 90% in trials with risk stratification by biological features of leukaemic cells and response to treatment, treatment modification based on patients' pharmacodynamics and pharmacogenomics, and improved supportive care. However, innovative approaches are needed to further improve survival while reducing adverse effects. Prognosis remains poor in infants and adults. Genome-wide profiling of germline and leukaemic cell DNA has identified novel submicroscopic structural genetic changes and sequence mutations that contribute to leukaemogenesis, define new disease subtypes, affect responsiveness to treatment, and might provide novel prognostic markers and therapeutic targets for personalised medicine.

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Conflict of interest statement

Conflicts of interest statement

HI receives unrelated research support from Bayer/Onyx.

Figures

Figure 1
Figure 1
Composite causality of childhood ALL. 1) Exogenous (eg, infection) and endogenous (eg, inflammation, oxidative stress) exposures, 2) normal allelic variation in inherited genes, and 3) chance all play roles in 4) the covert natural history of childhood ALL,,, leading ultimately to 5) overt disease and clinical diagnosis. Cancer causation is riddled with chance, for example, incidental “external” exposure, incidental damage to a relevant oncogene in a relevant cell (stem or progenitor cell), and chance events at conception involving parental gene shuffling and recombination.
Figure 2
Figure 2
Cytogenetic and molecular genetic abnormalities in childhood ALL. ALL with rearrangement of CRLF2 but without the BCR-ABL1-like transcriptional profile rarely presents with other classifying karyotypic alterations but may be seen with high hyperdiploidy. The dicentric cases may have a range of heterogeneous translocations, including classifying translocations (eg, ETV6-RUNX1). iAMP21, intrachromosomal amplification of chromosome 21.
Figure 3
Figure 3
Schema of genetic pathogenesis of B-ALL at diagnosis and relapse. HSC, hematopoietic stem cell; RAG, recombinase activating gene.
See this image and copyright information in PMC

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