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J Adolesc Young Adult Oncol. 2011 Jun;1(2):77-86.

Advances in the Biology of Acute Lymphoblastic Leukemia-From Genomics to the Clinic.

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1
Department of Pathology, St. Jude Children's Research Hospital , Memphis, Tennessee.

Abstract

Despite impressive advances in cure rates for childhood acute lymphoblastic leukemia (ALL), ALL remains the leading cause of disease-related death in young people and new therapeutic approaches directed against rational therapeutic targets are urgently required to improve treatment outcomes. This is particularly true for ALL in older children, adolescents, and adults, in whom treatment outcomes are markedly inferior to those of young children. A major goal of current leukemia research is to use comprehensive genomic analysis of the leukemic cell genome, transcriptome, and epigenome to identify critical new genomic alterations that drive leukemogenesis and influence responsiveness to therapy. Genomic analyses in childhood ALL have been remarkably informative and have identified a number of new structural genetic alterations that play important roles in the establishment of the leukemic clone and determine risk of relapse. Notably, many high-risk ALL cases harbor loss-of-function and dominant mutations of genes that encode transcriptional regulators of lymphoid development coupled with mutations that result in activation of cytokine receptor and kinase signaling pathways. These advances have resulted in new diagnostic approaches and therapeutic trials in ALL. This review will discuss these advances and outline challenges for future studies, including the potential role of genome-wide sequencing approaches and the need for detailed studies of the genetics of ALL in the adolescent and young adult population.

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