Role of protein tyrosine phosphorylation in chronic lymphocytic leukemia cell apoptosis

Abstract

Chronic lymphocytic leukemia (CLL) is a malignant disorder characterized by the proliferation and accumulation of mature appearing, though dysfunctional lymphocytes. The malignant lymphocytes infiltrate the bone marrow, lymph nodes, liver and spleen, resulting in enlargement of these organs and in bone marrow failure. In the present study, we investigated the role of tyrosine phosphorylation in CLL cell apoptosis. A cell line (WSU-CLL) derived from a CLL patient and the lymphocytes from several CLL patients and healthy volunteers were used to explore the role of protein tyrosine phosphorylation and its related signaling. Since tyrosine phosphorylation is important in lymphocyte signaling, including cell proliferation, differentiation and apoptosis, defects in tyrosine phosphorylation may contribute to the clonal expansion of this neoplasm. Tyrosine phosphorylation is maintained by a balance between the activities of the protein tyrosine kinases and phosphatases. We hypothesized that the inhibition of protein tyrosine phosphatase by vanadate would increase protein tyrosine phosphorylation and apoptosis in CLL cells. (Abstract shortened by UMI.)