Molecular profiling in multiple myeloma
Multiple Myeloma (MM) is a malignant plasma cell disorder accounting for 1% of all malignant diseases and 10% of hematological malignancies. The annual incidence world-wide of MM is approximately 0.4 to 5 per 100.000, with high incidence rates in North America, Australia/New Zealand, Northern Europe, and Western Europe compared with Asian countries. Within the United States, the incidence in African Americans is about double that in Caucasians, whereas persons of Japanese and Chinese origin have lower rates. In the Netherlands the annual incidence of MM is 5 per 100.000 and increases progressively with age, the median age of diagnosis is 70 years. MM is characterized by clonal expansion of malignant plasma cells in the bone marrow. The myeloma plasma cell is a post-germinal centre plasma cell which has undergone somatic hypermutation and immunoglobulin class switching. MM cells secrete a monoclonal protein (M-protein) which can be detected in serum and/or urine. The M-protein is IgG in 50% of patients, and IgA in 30% of patients or consists of light chain (15%). In rare cases, secretion of IgD (1%–2%), IgM (0.2%), or IgE (even less frequent), or absence of secretion (non-secretory MM) is found. Osteolytic bone lesions are the hallmark of MM. Other characteristic clinical features include renal injury, anemia, hypercalcemia and immunodeficiency with recurrent infections. These features may result directly from mass accumulation of plasma cells in tissues (plasmacytomas) or indirectly from effects of the M-protein and/or cytokines secreted by the plasma cells. Furthermore a high level of M-protein can cause hyperviscosity, renal failure and neuropathy.
|Publisher||Erasmus MC: University Medical Center Rotterdam|
|Promotor||Sonneveld, P. (Pieter)|
|Sponsor||The studies described in this thesis were supported by the Dutch Cancer Foundation Queen Wilhelmina (KWF), European Hematology Association (EHA) clinical research grant, International Myeloma Foundation (IMF), Erasmus MC, German Federal Ministry of Education and Research, Myeloma Stem Cell Network (MSCNET), Center for Translational Molecular Medicine (CTMM) and Janssen. And a personal donation by Mr. P. Plaisier. Publication of this thesis was financially supported by: Janssen, Novartis, Mundipharma, Amgen, Celgene, and Fonds Stimulans|
|Keywords||Kahler disease, multiple myeloma|
Broyl, A.. (2012, November 7). Molecular profiling in multiple myeloma. Erasmus MC: University Medical Center Rotterdam. Retrieved from http://hdl.handle.net/1765/37640