Uncovering the role of HMG box protein TOX in T-cell Acute Lymphoblastic Leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes. Despite improved therapy, relapsing pediatric patients have less than a 30% survival rate. It is therefore important to identify new drug targets for treatment of relapsed T-ALL. In this project,TOX, which is over-expressed in human T-ALL was studied for modulating T-ALL pathogenesis. Through a zebrafish transgenic screen, Tox was shown to act as a collaborating oncogene that increased T-ALL aggression. Data suggest that Tox over-expression results in a HOX11 signature characteristic of rapid cell division, and likely induces molecular pathways in T-ALL pathogenesis unlike T-ALLs expressing only Myc. Uncovering the TOX-regulated molecular pathways may help identify novel drug targets for T-ALL treatment