Abstract
Contemporary chemotherapy protocols have improved cure rates for children, adolescents, and young adults (CAYA) with T-lineage acute lymphoblastic leukemia (T-ALL) to greater than 80%. Unfortunately, outcomes for CAYA with relapsed and refractory disease, as well as older adults, remain poor. A key goal in the treatment of T-ALL therapy is preventing relapse; however, it is challenging to identify high-risk patients. Recently, several genomic initiatives have identified distinct biological subtypes of T-ALL and have correlated disease biology, including mutational status, transcriptional phenotype, and clonal drivers, with therapy response and outcome. The integration of genomic profiling into clinical diagnosis and treatment has promise to guide risk stratification, targeted therapy, and clinical trial design for high-risk patients. This review highlights the recently mapped genomic landscape of T-ALL, with particular emphasis on recently identified genomic molecular signatures, their utility in risk stratification, and targeted therapy selection for refractory cases.