Does catalytic activity of Bence-Jones proteins contribute to the pathogenesis of multiple myeloma?

Some Bence-Jones proteins have been found to be capable of hydrolyzing DNA, chromogenic amide substrates, such as benzoylarginine p-nitroanilide, and natural oligopeptides, such as arginine vasopressin. Patients who excrete B ence-Jones protein with the DNA-nicking activity have shown moderately seve re symptoms. When incubated with LLC-PK1 (porcine kidney proximal tubule) c ells, some Bence Jones proteins penetrated the cytoplasm, and entered the n ucleus with little or no degradation of epitopes. Intranuclear Bence Jones proteins ultimately induced DNA fragmentation in situ and cell death. This cytocidal activity was not directly associated with the DNA-nicking activit y, since Bence Jones proteins with no detectable DNase activity also produc ed cell death. These results, however, suggest that the biological activiti es of Bence Jones proteins described here makes a significant contribution to the development and/or deterioration of multiple myeloma.