miércoles, 29 de diciembre de 2010
Curr Opin Pediatr. 2010 Dec 16. [Epub ahead of print]
How new advances in genetic analysis are influencing the understanding and treatment of childhood acute leukemia.
Roberts KG, Mullighan CG.
Department of Pathology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
PURPOSE OF REVIEW: This review describes the recent advances in genomic profiling that have provided critical new insights into the biology of acute leukemia in children.
RECENT FINDINGS: Acute leukemia genomes commonly harbor submicroscopic gains and deletions of DNA which target key cellular pathways that influence leukemogenesis and the likelihood of treatment failure, particularly in acute lymphoblastic leukemia (ALL). Notably, genetic alterations targeting transcriptional regulators of lymphoid development are a hallmark of B-progenitor ALL, and alteration of specific genes in this pathway, such as IKZF1 (encoding IKAROS), are associated with high-risk ALL. Integrated genomic profiling has identified potential therapeutic targets in ALL, including aberrant cytokine receptor signaling mediated by rearrangements and mutation of CRLF2 and JAK2. Genome-wide association studies are also providing important insights into the role of inherited genetic variation and susceptibility to ALL. In contrast, genomic profiling of acute myeloid leukemia (AML) has thus far yielded fewer insights, but ongoing resequencing of leukemia genomes is uncovering novel mutations in both ALL and AML.
SUMMARY: Genomic profiling has identified important new genetic lesions that contribute to leukemogenesis. These findings will have important implications for the development of new diagnostic tests and treatment approaches in high-risk leukemia. Future studies will be increasingly reliant on comprehensive genomic sequencing to reveal the spectrum of genetic alterations in this disease, with the ultimate aim of improving the treatment outcome for leukemia patients.
PMID: 21169835 [PubMed - as supplied by publisher]
How new advances in genetic analysis are influenci... [Curr Opin Pediatr. 2010] - PubMed result