Genetic and Epigenetic Profiles in T-ALL

T-cell acute lymphoblastic leukemia (T-ALL) accounts for around 15% of all pediatric leukemias. The molecular events driving leukemogenesis in this subgroup involve the activation of mutually exclusive transcription factors, which are generally present clonally in all leukemia cells. Additionally, there are secondary, commonly subclonal events resulting in the activation of oncogenes and the inactivation of tumor suppressor genes, leading to the activation of proleukemic signaling pathways and other oncogenic mechanisms. Prognostic subgroups have been defined based on the integration of molecular and clinical information, but translating this knowledge into successful new treatment strategies for resistant and relapsed T-ALLs remains challenging. Future clinical studies will thus have to consider several additional confounding factors including the active proteome, combinatorial effects of different leukemogenic mechanisms, and the subclonal architecture of leukemias. Given the rarity of this clinical entity, especially in its molecularly defined subgroups, future clinical studies will require urgent international collaboration.