Genomic Analysis Drives Tailored Therapy in Poor Risk Childhood Leukemia
ABSTRACT Ph-like acute lymphoblastic leukemia (ALL) is a novel subgroup of high-risk childhood ALL. In this issue of Cancer Cell, Roberts et al. describe the identification of genetic alterations that lead to activated kinase and cytokine receptor signaling in Ph-like ALL and demonstrate that this aberrant signaling can be inhibited effectively.
SourceAvailable from: April Ewton[Show abstract] [Hide abstract]
ABSTRACT: Chromosomal rearrangements including translocations, deletions, inversions, and insertions are common genetic alterations in cancer. Over 1,000 recurrent chromosome rearrangements have been reported so far in different human tumors (http://cgap.nci.nih.gov/Chromosomes/Mitelman). Most of these chromosome rearrangements are associated with specific tumor types and bear distinctive diagnostic and prognostic significance. Molecular characterization of these rearrangements has revealed numerous cancer genes, including novel fusion genes, and their normal and aberrant interactions involved in tumorigenesis, and has identified myriad therapeutic targets. With the help of advanced high-throughput technologies, many cryptic chromosome rearrangements undetectable by conventional cytogenetics have recently been discovered and delineated. The understanding of the mechanisms responsible for the formation of recurrent chromosome rearrangements and their biological functions has led to novel treatment regimens that target tumor cells specifically, with minimal impact to normal cells. Here, we review common recurrent chromosome rearrangements in both hematopoietic malignancies and solid tumors, and their clinical significance, with a focus on acquired fusion genes and their therapeutic implications (i.e., pharmacogenetics).06/2013; 1(2). DOI:10.1007/s40142-013-0011-9