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Type: Journal article
Title: Genomics in acute lymphoblastic leukaemia: insights and treatment implications
Author: Roberts, K.
Mullighan, C.
Citation: Nature Reviews Clinical Oncology, 2015; 12(6):344-357
Publisher: Nature Publishing Group
Issue Date: 2015
ISSN: 1759-4782
Statement of
Kathryn G. Roberts and Charles G. Mullighan
Abstract: 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.
Keywords: Chromosomes, Human, Pair 21
Receptors, Cytokine
DNA, Neoplasm
Gene Expression Profiling
Sequence Analysis, DNA
Epigenesis, Genetic
Gene Amplification
Gene Rearrangement
Child, Preschool
Genes, Neoplasm
Janus Kinases
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Genetic Variation
Young Adult
Transcriptional Regulator ERG
Rights: © 2015 Macmillan Publishers Limited. All rights reserved
DOI: 10.1038/nrclinonc.2015.38
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