Notch, a unifying target in T-cell acute lymphoblastic leukemia?

The expression of both Notch3 and pre-T-cell-receptor (pre-TCR) invariant chain appears to be a common feature of all T-cell acute lymphoblastic leukemias (T-ALL). Notch genes, and other genes that are dysregulated in some T-ALL subgroups, encode factors that play a crucial role in both T-cell development and leukemogenesis. A complex network of signals, involving Notchs, pre-TCR, nuclear factor kappaB and E2A, appears to be responsible for the leukemogenesis process. Thus, T-ALL is a paradigm for developmental pathways that underlie the pathogenesis of this disease.