T cell acute lymphoblastic leukemias (T-ALLs) arise from the malignant transformation of hematopoietic progenitors primed toward T cell development, as result of a multistep oncogenic process involving constitutive activation of NOTCH signaling and genetic alterations in transcription factors, signaling oncogenes, and tumor suppressors. Notably, these genetic alterations define distinct molecular groups of T-ALL with specific gene expression signatures and clinicobiological features. This review summarizes recent advances in our understanding of the molecular genetics of T-ALL.

T cell acute lymphoblastic leukemias (T-ALLs) are aggressive hematologic tumors resulting from the malignant transformation of T cell progenitors. T-ALL accounts for 10%–15% of pediatric and 25% of adult ALL cases (1) and is characteristically more frequent in males than females. Clinically, T-ALL patients show diffuse infiltration of the bone marrow by immature T cell lymphoblasts, high white blood cell counts, mediastinal masses with pleural effusions, and frequent infiltration of the central nervous system at diagnosis. Although originally associated with high relapse rates, the prognosis of T-ALL has gradually improved with the Introduction of intensified chemotherapy, with cure rates in modern protocols reaching over 75% in children and about 50% in adults with this disease (2). However, the outcome of T-ALL patients with primary resistant or relapsed leukemia remains poor (3, 4). Therefore, current research efforts are focused on the search for targets for the development of more effective and less toxic antileukemic drugs (5), which will likely require a greater degree of specificity and an improved understanding of the molecular events that lead to the disease.