Clinical Studies Resource Centre Member Ontario Cancer Institute (OCI)
Dr. Messner directs the clinical Bone Marrow Transplant (BMT) program. One of the major goals is to understand mechanisms that lead to the control of hemopoietic malignancies by BMT. This is approached in clinical and laboratory studies.
Dr. Messner is interested in the evaluation of early hemopoietic progenitors in cell culture. Culture assays are available for multipotent progenitors and precursors restricted to a single hemopoietic lineage. The assays are used to identify and characterize cell populations in the bone marrow and peripheral blood that are essential for the engraftment process in bone marrow transplant recipients.
In addition, the culture systems are used as bioassays for growth promoting activities that are produced by BMT recipients following administration of their preparative regimen and infusion of bone marrow. These studies are designed to improve the engraftment process in clinical BMT.
His second interest is related to the development of methods to study minimal residual disease in BMT recipients. Two model systems are currently under study. The laboratory was successful in raising a number of cell lines from patients with malignant Iymphoma and multiple myeloma. These lines are used to investigate whether or not malignant cell populations require growth factors to stimulate their proliferation.
These investigations have demonstrated heterogeneity with respect to factor requirement. They have also shown that malignant populations derived from some patients produce their own factors. Genetic changes of p53 and c-myc are currently under study as potential mechanism for altered growth.
The populations of malignant B-lymphocytes can be readily identified for each individual patient using molecular approaches. The system is used to evaluate whether or not BMTs are successful in ablating the malignant clones.
The second model of study is chronic myeloid leukemia. Residual disease after BMT can be identified using PCR for the characteristic abl/bcr translocation. Mechanisms are under examination to determine how this population of cells can be controlled.