Acute lymphoblastic leukemia (ALL) is the commonest childhood tumor and a leading cause of cancer related death in young people. The last decade has witnessed intense activity in the field of ALL genomics, initially with microarrays and more recently with next generation sequencing, with the goal of comprehensively identifying all genetic alterations contributing to leukemogenesis, treatment failure and relapse. These studies have defined new entities of ALL, and have shown that each ALL subtype is typically defined by constellations of recurring chromosomal alterations and sequence mutations that target key cellular pathways including lymphoid maturation, cellular proliferation, tumor suppression, and chromatin modification. Genomic profiling has also identified genetic alterations that have clear implications for leukemia diagnosis and therapy in several subtypes of high-risk leukemia, including early T-cell precursor ALL, hypodiploid ALL, and BCR-ABL1-like ALL. Several genetic alterations are associated with an increased risk of leukemia relapse, including IKZF1, CREBBP, and NT5C2. Moreover, studies interrogating germline genetic variation have identified common variants associated with leukemia susceptibility, including risk of specific subtypes of ALL and ALL in different ethnic groups, and inherited mutations in familial ALL. Ongoing efforts are completing the genomic characterization of the spectrum of ALL cases, dissecting the genetic basis of clonal heterogeneity of ALL, and expanding these studies into integrated analysis of structural variation with the leukemia epigenome and transcriptome.

Citation Format: Charles Mullighan. The genomic landscape of acute lymphoblastic leukemia. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr IA23.