Expression of p56^lck in B-Cell Neoplasias

Abstract

The protooncogene p56^lck is considered to participate in malignant transformation of lym-phoid cells. In order to evaluate the role of this tyrosine kinase in B cell neoplasias, we investigated the expression of p56^lck by Western blot analysis. In 12/16 Burkitt's lymphoma derived cell lines, 3/3 lymphoblastoid cell lines, 1/6 Hodgkin's disease derived cell lines, and 10/10 freshly isolated chronic lymphocytic leukemia cells constitutive expression of the protein was detected. Protein tyrosine kinase assays detected a catalytic active form of p56^lck in all p56^lck expressing samples. Stimulation experiments of the different cell lines and primary tumour cells by the phorbol ester TPA and the B-cell specific stimulation with SAC/anti-IgM respectively indicated a change of the expression level in comparison with the unstimulated cells and, a higher molecular weight species of the protein tyrosine kinase p56^lck was observed. This was probably due to hyperphosphorylation of p56^lck.

No correlation between an infection with the Epstein-Ban virus and the expression of p56^lck was found in the cell lines used and in primary tumour cells. Inhibition of p56^lck activity by the specific inhibitor 4-amino-6-hydroxyflavone revealed a decrease of proliferation of the T-cell line Jurkat, but not of the Burkitt's lymphoma cell lines. In the analysed cell lines we found a reduction of the kinase activity of p56^lck of approximately 70%. These results suggest that lck may contribute to the maintenance of the transformation of the analysed B cell neoplasias but that lck does not support a model for an initial event in B cell transformation.

Key Words:

• p56^lck
• B-cell neoplasias