The role of BRWD2/PHIP as a novel epigenetic tumor suppressor in T-cell acute lymphoblastic leukemia and lymphoma

T-lineage acute lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) are aggressive hematologic malignancies that require treatment with intensified chemotherapy. Studies of the long-term effects of chemotherapy in patients with T-ALL/T-LBL showed that recent gains in leukemia-free survival have been achieved at the cost of significant increases in the rates of lifethreatening and debilitating toxicities. More than 40 years ago, recurrent deletions of the long arm of chromosome 6 (6q) were identified in tumor cells from T-ALL and T-LBL patients. However, as off today, the underlying molecular target of these 6q deletions remains completely unknown. In this project, we will investigate how BRWD2/PHIP, an epigenetic regulator located on 6q, acts as a novel tumor suppressor gene in the pathogenesis of human T-ALL/T-LBL. Novel insights into how loss of BRWD2/PHIP affects the chromatin architecture should provide opportunities for the development of novel targeted therapies for T-ALL/T-LBL.