Childhood acute lymphoblastic leukemia: Integrating genomics into therapy

Acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, is a genetically complex entity that remains a major cause of childhood cancer‐related mortality. Major advances in genomic and epigenomic profiling during the past decade have appreciably enhanced knowledge of the biology of de novo and relapsed ALL and have facilitated more precise risk stratification of patients. These achievements have also provided critical insights regarding potentially targetable lesions for the development of new therapeutic approaches in the era of precision medicine. In this review, the authors delineate the current genetic landscape of childhood ALL, emphasizing patient outcomes with contemporary treatment regimens as well as therapeutic implications of newly identified genomic alterations in specific subsets of ALL. Cancer 2015;121:3577–3590. © 2015 American Cancer Society. Advances in the genomic characterization of childhood acute lymphoblastic leukemia have led to modern risk‐stratification and chemotherapeutic modifications for specific subsets of patients. The incorporation of molecularly targeted agents into therapy has significantly improved or has the potential to improve outcomes for patients with high‐risk acute lymphoblastic leukemia.