T-Cell Acute Lymphoblastic Leukemia: A Cytogenomic Update

T-cell acute lymphoblastic leukemia (T-ALL) is a pervasive hematologic malignancy that arises from developmental and genetic abnormalities manifested in lymphoblasts belonging to the T-cell lineage. Responsible for 10-15% of pediatric acute lymphoblastic leukemia (ALL) and 25% of adult ALL patients, T-ALL is characterized not only by cytomorphic features, but also by the aberrant expression of specific genes critical to T-cell development. Such changes in the genome ultimately result in mutational and developmental cascades that alter the chromosomal constitution, the process of which are used to organize T-ALL cases into different subgroups according to specific gene expression signatures. Clinically, comprehensive categorizations are important in risk stratification, assessment, and treatment protocols. Notable genetic subgroups include that of TAL, TLX1, TLX3, HOXA, MYB, ETP and NKX2. Current research also recognizes phenotypic and immunologic categories, such as ALK-positive ALCL, ALK-negative ALCL, BIA ALCL, AITL, and PTCL, NOS, which has revolutionized our understanding of T-cell lymphoma. Furthermore, it has been suggested that most T-ALL patients present with abnormal NOTCH1 genes in addition to mutations involving the JAK-STAT signaling pathway. These abnormalities are associated with the regulatory malfunction of T-cell development as well as that of their respective tumor suppressors and oncogenes. While recent studies have revealed characteristic defects in T-ALL, the interactions between oncogenes and their tumor suppressors with leukemia development are not well known as the signaling pathways involved behind each genetic lesion have yet to be fully explored. Studies involving FISH, RT-PCR, aCGH, and NGS offer novel perspectives to potentially learn more about the pathogenesis and cytogenetics of T-ALL, a field that demands further attention and research.