Role of the hedgehog pathway in the development of T-cell aculte lymphoblastic leukemia.

The hedgehog signaling pathway plays an important role in cell growth and differentiation and is involved in the development of many tissues, including T cell development. Studies have revealed mutation of this pathway in solid tumors, but not in hematological malignancies. Upon mutation analysis of 97 candidate oncogenes in T-cell acute lymphoblastic leukemia (T-ALL), we identified point mutations in several genes encoding important signaling proteins of the hedgehog pathway. We identified mutations in 7 of 17 (41%) cell lines and 9 of 57 (15%) primary T-ALL samples. In addition, we observed that the proliferation of T-ALL cell lines was inhibited by various hedgehog pathway antagnosists. In this project, we aim to study the role of the hedgehog pathway in the development of T-ALL in more detail, both at the genetic and functional level. We will sequence more T-ALL samples to obtain a better view on the possible association of hedgehog pathway mutations with clinical characteristics. Second, we plan to use cell models and mouse models to determine the exact contribution of the hedgehog pathway to the development of leukemia. Finally, we aim to study the potential of hedgehog pathway antagonists as a novel therapeutics for the treatment of T-ALL.

Keywords:Lymphoblastic leukemia

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences