Alterations in Wnt Signaling in CALM-AF10 Translocated Leukemia
Mentor Name: Jessica Heath
Leukemia is the most common childhood cancer. While some leukemias respond well to standard chemotherapy, others become resistant, resulting in relapse of disease and poor outcomes. We study an aggressive childhood leukemia, which is characterized by the presence of an abnormal protein called CALM-AF10. We have found that the CALM-AF10 protein alters the activation of the Wnt pathway which is known to be important in the development of some types of leukemia. The are multiple components of the Wnt pathway, including a protein called beta-catenin. AF10 has been found to interact with beta-catenin in other cell types. It is not known whether these proteins interact in leukemia cells, nor whether the presence of the abnormal CALM-AF10 protein impacts that interaction. We will determine whether AF10 physically interacts with beta-catenin in leukemia cells, whether the presence of CALM-AF10 impacts this protein-protein relationship, and whether CALM-AF10 alters the localization of beta-catenin with a cell. We will further examine the impact of CALM-AF10 on Wnt signaling in a comprehensive way. These studies will set the stage for future work aimed at understanding the role of beta-catenin and the Wnt pathway in CALM-AF10 leukemia, as well as the potential therapeutic potential of targeting components of this pathway in these high-risk malignancies.
