Mar 18, 2015

Genomics in acute lymphoblastic leukaemia: insights and treatment implications

Nature Reviews. Clinical Oncology
Kathryn G Roberts, 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 h...Continue Reading

Mentioned in this Paper

Chromosomes, Human, Pair 21
Genome-Wide Association Study
Leukemia, Lymphocytic, Acute, L2
Study
Biochemical Pathway
Microarray Analysis
Morbidity Aspects
Hematologic Neoplasms
Gene Amplification
Genome

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