Genetic Alterations of Pediatric Acute Lymphoblastic Leukemia

Abstract

Recent genetic studies of pediatric acute lymphoblastic leukemia (ALL), both in B cell precursor and T cell ALL (B/T-ALL), clarified the landscape of genetic alterations due to great progress of comprehensive genome sequencing technologies including next generation sequencing. These studies revealed genetic alterations such as somatic structural DNA rearrangement and sequence mutations that affect multiple pathways including lymphocyte development, cytokine signaling, JAK-STAT pathway, MAP kinase and RAS signaling pathway, transcriptional, and epigenetic regulation to provide us new insight of leukemogenesis of pediatric B/T-ALL. In addition, recent comprehensive genetic studies of paired diagnostic and relapse samples clarified the mechanism of clonal evolution of leukemic cells to provide novel insights of mechanism of therapeutic resistance of pediatric ALL. Owing to huge success of genetic studies, several new subtypes of pediatric ALL have been identified, and some of them are clinically important to be candidate of targeted therapy. Here, we provide a review of recent genetic studies of pediatric ALL including B/T-ALL, acute leukemia ambiguous lineage, and relapsed ALL and discuss the importance of genetic basis of pediatric ALL.