Ikaros in T-Cell Leukemia

Although extensive clinical data have established that the loss of Ikaros tumor suppressor activity via genetic inactivation is a major contributor to leukemogenesis leading to B-cell ALL, less is known about the role of Ikaros in T-cell leukemia. The T-cell malignancies observed in Ikaros-deficient mice suggest that Ikaros is likely to function as a tumor suppressor in T-cells. In human, multiple studies have identified genetic inactivation of Ikaros (deletion or mutation) to be associated with ~5% of T-ALL cases. Additional studies provide evidence that the functional inactivation of Ikaros due to defects in signal pathways that normally regulate Ikaros activity is likely to be a critical factor in the development of Tcell malignancies. These studies provide a rationale for new chemotherapeutic strategies in the treatment of T-cell leukemia. In this chapter, we summarize the newest advances that shed light on the role of Ikaros in T-cell leukemia.