Genetic and epigenetic aberrations of pediatric leukemia and clinical applications

Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Although fusion genes generated by chromosomal rearrangements are the most frequent genetic alterations in pediatric ALL, fusions are insufficient for the development of this disease, and thus, cannot serve as therapeutic targets for ALL. Recently, integrated genetic analysis using next generation sequencing technology has revealed the genetic landscapes of pediatric ALL. These studies disclosed that in addition to fusion genes, aberrations of cell proliferation pathways and epigenetic regulations are also involved in the pathogenesis of pediatric ALL. On the other hand, more recently, abnormalities of supper enhancer regions of TAL1 have been detected as a novel oncogenic mechanism of pediatric T cell ALL. Furthermore, germline mutations of ARID5B, PAX5, and GATA3 have been found to be involved in the genetic risk of developing ALL. Therefore, currently, the molecular mechanisms of pediatric ALL have been fully disclosed.