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Multiple myeloma

Multiple myeloma is the uncontrolled growth of plasma cells. Plasma cells are B lymphocytes specialized for production of immunoglobulines. Multiple myeloma originates in B lymphocytes of germinal centers in lymphoid tissue of the spleen and lymph nodes.  

A characteristic of multiple myeloma is the increase of monoclonal plasma cells in the bone marrow, which produce monoclonal gammaglobulin (paraprotein), or sometimes only light or heavy monoclonal chains. 

Plasma cells produce immunoglobulins, each clone their own immunoglobulin. A plasma cell clone which grows uncontrollably can produce large amounts of immunoglobulin. This can be diagnosed using electrophoresis of serum or urine as a peak in the gamma region and is described as the M-component (monoclonal component). The M-component is an indirect indicator of the activity/size of the clone and is important for the diagnosis and evaluation of treatment response.

When myeloma cells proliferate in the bone marrow, they may displace the production of normal blood cells and lead to low hemoglobin (anemia), reduced immune defense (enhanced susceptibility to infections), or low number of thrombocytes (increased risk of bleeding). They may also displace the compact tissue of the bone marrow and give rise to areas of low bone density (osteolytic lesions) which may lead to fractures. The immunoglobulin produced by the myeloma cells can have various properties. Some of these proteins can give rise to depositions in tissues and may, for instance, influence the renal function.

The disease is progressive and is often diagnosed before symptoms develop. Curative treatment for myelomatous disease is not available. But since the milennium, several new drugs have given hope of better control of the disease and longer survival. On average, it takes one to three years for asymptomatic multiple myelomas to develop into a symptom-causing disease.

Cytokine production in the disease process mutually influences the various bone marrow cells: between malignant plasma cells, stroma cells, osteoblasts, and osteoclasts. This causes expansion of the malignant clone, osteolysis, and eventually pathological fractures with significant pain.

Additional mutations with activation of oncogenes, loss of tumor suppressor genes, and suppression of apoptosis facilitates spreading of tumor cells. Simultaneously, the production of normal hematopoetic tissue is suppressed which eventually leads to bone marrow failure and pancytopenia.

Incidence 

In 2013, there were 380 new cases of multiple myeloma diagnosed (1) in Norway. The disease is slightly more frequent in men than women. About 15% of the patients are < 60 years and about 25 % are between 60–65 years. Less than 2 % are < 40 years at the time of diagnosis.

 

Age-specific incidence of multiple myeloma, 2009–2013.

Source: Cancer Registry of Norway

 

 

Incidence of cancer of multiple myeloma, 1954–2013.

Source: Cancer Registry of Norway

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