Compared to some more common cancers, multiple myeloma generates few headlines, but it is a killer that afflicts about one million people worldwide and so far has resisted the best efforts of medical science to defeat it.
Myeloma has long been understood as a cancer of the hones, and indeed it is here, in the hone marrow, that the disease runs its deadly course. Now", U of A researchers Linda Pilarski and Andy Belch are looking beyond the bones to understand the origins and spread of the disease. Pilarski, a basic researcher, a former immunology professor, or whose interest in myeloma has taken her to an appointment in oncology and an office in the Cross Cancer Institute, where she collaborates with Belch, a clinician and professor of oncology.
Multiple myeloma is characterized by uncontrolled growth of plasma cells in the bone marrow. Normally plasma cells—the body's factory for producing antibodies — make up less than five per cent of the cells in the bone marrow. When they proliferate (sometimes climbing to as high as 90 per cent of marrow cells) they upset the body's chemical balance. The consequences can include kidney failure, thickening of the blood, and a weakening of the themselves cus of mycloma Belch were inspired to look elsewhere. Plasma cells, explains Belch, have a propensity to stay put in the marrow. Flowever, myeloma patients typically have multiple lesion sites, in which the malignant cells can all be shown to have a common origin. And that, he says, points to a "very, very active" process of spread. About 10 years ago, Pilarski and immune system — many myeloma patients die of opportunistic infections.
While the malignant plasma cells have long been the foresearch, Pilarski and Belch noted the presence of many highly abnormal B cells in the blood of tnyeloma patients and speculated that these abnormal cells eventually migrated to the bone marrow to give rise to the disease. They have since shown that these abnormal B cells are, in fact, malignant and have the identical molecular genetic rearrangement as the plasma cells of the same patient — strong evidence that they are involved in the spread of the disease. (And because these cells are, for the most part, resistant to treatments targeting plasma cells, it would explain why there is so little correlation between the destruction of malignant plasma cells and control of the disease.)
Their research has already led to a test for monitoring myeloma that is being commercialized, and Pilarski and Belch are now working on the development of new treatment protocols that will target the malignant B cells based on some unique biological properties of these cells. The researchers believe that the most promising treatment approach may be to somehow reimpose the immune system's control over the abnormal cells. "All of us may have malignant B cells, but as long as they are held dormant by regulatory T cells they are harmless," says Pilarski.
She speculates that myeloma results when somehow the T -cell control is lost. "If we could therapeutically re-establish regulatory control over the myeloma clones, patients could safely coexist with their cancer, perhaps permanently."
Published Winter 1999.