Genome-wide Studies in Childhood Acute Lymphoblastic Leukemia

The convergence of multiple genome-wide platforms for molecular studies allows exceptionally high-resolution interrogation of the total complement of genetic and epigenetic alterations of the cancer cell. The influence of inherited host pharmacogenomics on drug responsiveness can likewise be examined in a high-throughput manner with single-nucleotide polymorphism (SNP) profiling. Childhood acute lymphoblastic leukemia (ALL) is easily investigated by modern genomic tools. Gene-expression patterns can classify ALL into various known and novel subtypes. Within these subtypes, multiple genomic lesions have been systematically characterized and have identified abnormalities in major pathways, including cell-cycle regulation, lymphoid differentiation and signaling, regulation of apoptosis, and tumor suppression. Clinically important phenotypes such as early response to therapy, long-term outcome, and development of adverse events have been correlated to genes and pathways identified in integrated analyses of the genome and transcriptome, providing valuable information for improved risk stratification. Uncovering the molecular mechanisms responsible for therapy failure will lead to strategies to circumvent resistance and to the development of biologically based targeted therapies.