Molecular aspects of multiple myeloma

Multiple myeloma (MM) is a malignant proliferating disorder of the B lymphocyte lineage, characterized by an increasing proportion of plasma cells in the bone marrow, a high and progressively increasing concentration of a homogeneous immunoglobulin in the blood and the occurrence of osteolytic bone lesions. It is predominantly a disease of the elderly. The incidence of MM in the Netherlands is approximately 3 in 100,000 inhabitants. The prognosis for survival is about 3 years. In this thesis a study was made of genetic defects responsible for the transforming event in MM. The purpose of this study was to increase our insight into the underlying mechanism of tumor formation and to find tumor specific markers that would improve the diagnosis MM in an early stage of the disease. Since the discovery of oncogenes in the early eighties, much progress has been made in understanding tumor development. Oncogenes can play an important role in the process of malignant transformation. Oncogenes are activated proto-oncogenes, which in normal cells regulate growth and differentiation. Alterations in such genes by translocations, amplifications, point-mutations or deletions can disturb the normal growth pattern of the cell leading to malignant conversion