Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases

Significance We provide transcriptomic insights into differences between pediatric and adult T cell acute lymphoblastic leukemia (T-ALL) patients through an international collaborative effort integrating RNA-sequencing data of 707 patients. Ten subtypes were identified, each characterized by distinct gene mutation profiles and dysregulated expression signatures of leukemogenic factors, and associated with T cell development stages. Adult T-ALL tends to have characteristics of early T cell precursor ALL, mostly corresponding to the mixed phenotype acute leukemia, whereas pediatric T-ALL shows a wide spectrum of aberrant molecular features, from early T cell precursor to mature T cell compartments. Our findings have important implications for disease mechanism of T-ALL that differs between pediatric and adult patients, facilitating further refined targeted therapy.