Novel insights into the development of T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) results from malignant transformation of immature cells of the T-cell lineage. T-ALL is a heterogeneous disease both clinically and genetically. It is generally accepted that T-ALL cells are the malignant counterpart of normally developing T cells in the thymus (thymocytes). Recent data using genome-wide gene expression profiling and assessment of the rearrangement status of the T-cell receptor loci confirm this notion. T-ALL cells differ from normal thymocytes in the overexpression of oncogenes that arise either from chromosomal translocations or via other mechanisms. In addition, signaling pathways that control the very first stages of thymocyte development (of note, the Notch and Wnt pathways) are involved in development of T-ALL in mice and humans when constitutively expressed. In particular, the activating mutations in the Notch pathways are believed to occur in a large proportion of human T-ALL. These findings on genetic events open up new therapeutic possibilities.