Research Interests:

The major focus of my research has been to study the mechanisms of action of antitumor agents in chronic lymphocytic leukemia (CLL) and lymphomas, and to understand the factors involved in the production of drug resistance. Molecular and biochemical studies on leukemic or lymphoma cells obtained from patients are related to the patients' clinical course and response to therapy. We have been evaluating the molecular mechanisms involved in drug resistance and the rate of overexpression of p53, Bax, Bcl-2 and mdm-2 in CLL and aggressive non-Hodgkin's lymphomas. In collaboration with Dr. S. Mai, we have been examining genomic changes in CLL, in particular the unique observation that there is extrachromosomal amplification of the cyclin D2 gene. This change affects all cells in all patients suggesting that it is an early genomic change which may play a key role in the causation of this leukemia. Ongoing studies are examining how overexpression of cyclin D2 may be involved in the pathogenesis of CLL and in determining which other genes may be amplified in this leukemia.

Selected Publications:

1. Navaratnam S, Williams GJ, Rubinger M, Pettigrew NM, Mowat MR, Begleiter A, Johnston JB Expression of p53 predicts treatment failure in aggressive non-Hodgkin's lymphomas. Leuk. Lymphoma, 29:139-44, 1998. PMID 9638983
2. Liu, K.Z., Schultz, C.P., Mohammad, R.M., Al-Katib, A.M., Johnston, J.B., Mantsch, H.H. Similarities between the sensitivity to 2-cholorodeoxyadenosine of lymphocytes from CLL patients and bryostatin 1-treated WSU-CLL cells: an infrared spectroscopic study. Cancer Lett. 127:185-93, 1998. PMID 9619876
3. Deaninck, P.J., Williams, G.J., Rubinger, M., Johnston, J.B. Multiple myeloma presenting clinically as lymphoma. Leuk. Lymphoma, 28:195-201, 1997. PMID 9498720
4. Johnston, J.B., Daeninck, P., Verburg, L., Lee, K., Williams, G., Mowat, M.R.A., Israels, L.G. and Begleiter, A. P53, mdm-2, bax and bcl-2 and drug resistance in chronic lymphocytic leukemia. Leuk. Lymphoma 26:435-49, 1997. PMID 9389352
5. Begleiter, A., Mowat, M., Israels, L.G. and Johnston, J.B. Chlorambucil in chronic lymphocytic leukemia - mechanism of action. Leuk. Lymphoma, 23:187-201, 1996. PMID 9031099

Lab Members