Genomic and pharmacogenetic studies of childhood acute lymphoblastic leukemia

Abstract

With the cure rate of childhood acute lymphoblastic leukemia (ALL) approaching 90%, further improvement in the treatment outcome and quality of life of patients will require better understanding of the mechanisms of drug resistance, identifying new leukemic cell genetic lesions that are amendable to available target therapy, and optimizing treatment based on host pharmacodynamics and pharmacogenomics. Deeper characterization of leukemic cell genetic abnormalities has discovered new subtypes of leukemia such as early T-cell precursor ALL and Philadelphia chromosome-like ALL, and identified many genomic alterations that have diagnostic, prognostic, or therapeutic implications. In this regard, several novel fusion transcripts are responsive to ABL tyrosine kinase inhibitors and potentially to JAK inhibitors. Genome-wide analyses have also unraveled the role of inherited cancer predisposing genes and small nucleotide polymorphisms of several genes in the development of childhood ALL. These advances promise to lead to more sophisticated personalized treatment strategies in the near future.

Keywords

acute lymphoblastic leukemia / genomics / pharmacogenetics / pharmacogenomics

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Acknowledgements

This work is supported in part by the US National Institute of Health (Grant Nos. CA36401, CA21765 and GM92666) and American Lebanese Syrian Associated Charities (ALSAC).

Compliance with ethics guidelines

Ching-Hon Pui declares that he has no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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2014 Higher Education Press and Springer-Verlag Berlin Heidelberg