Douglas K. Graham, MD, PhD

Mer Tyrosine Kinase as a Cooperative Oncogene in Leukemogenesis

Tyrosine kinases are a family of proteins that are directly linked to multiple types of human cancer. Dr. Graham is investigating the role of a tyrosine kinase, Mer, in childhood T cell leukemia and lymphoma. The Mer protein is not expressed in normal lymphocytes but is expressed in many acute lymphoblastic leukemia (ALL) cell lines and patient samples. Dr. Graham’s lab has made a transgenic Mer mouse model which has abnormal Mer expression in lymphocytes (similar to the leukemia patient samples) and has found that the mice develop leukemia and lymphoma, suggesting a causative role of the Mer proto-oncogene. With the assistance of a grant from Gabrielle’s Angel Foundation for Cancer Research, Dr. Graham will clarify the role of Mer in cooperating with other oncogenes in leukemia development. Abnormal expression of Mer and oncogenes thought to be important in T cell leukemia will be evaluated from a national pediatric oncology cell bank. In addition, overexpression of known ALL oncogenes will be combined with Mer overexpression in mouse models to determine which oncogenes Mer may cooperate with to lead to leukemia or lymphoma. These studies will help lead to a better understanding of the biology of T cell leukemia and lymphoma, and will hopefully lead to new therapeutic targets for this disease.