Genetic insights in the pathogenesis of T-cell acute lymphoblastic leukemia

Over the past 20 years, a large number of genes involved in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) has been identified by molecular characterization of recurrent chromosomal aberrations and more subtle genetic defects. When reviewing the current list of oncogenes and tumor suppressor genes, it becomes clear that these can be grouped into four classes of mutations, which are involved in: (i) cell cycle deregulation; (ii) impaired differentiation; (iii) proliferation and survival advantage and (iv) unlimited self-renewal capacity. Based on recent studies of T-ALL, we can speculate that at least these four different mutations are required for the development of T-ALL. In this review we summarize our current insights into the molecular pathogenesis of T-ALL, and we discuss how these molecular findings provide new directions for future research and novel therapeutic strategies in T-ALL.