Origins of the Disease
Plasma cells are the final product in the life cycle of B lymphocytes (B cells), a type of white blood cell, which originates in the bone marrow and helps constitute the immune system. When a person develops an infection, B cells respond by rapidly maturing into plasma cells. These cells produce antibodies called immunoglobulins that help destroy infectious agents. Plasma cells are found in the tonsils, lymph nodes, abdomen, and bone marrow.
Multiple myeloma develops when a normal plasma cell is transformed into a malignant cell, one capable of uncontrolled growth and spread. This transformation results from genetic mutations -- changes in a cell's DNA -- that can occur as plasma cells divide. The malignant cell begins producing identical copies of itself called clones, binding to stromal cells, a type of connective tissue cell. Once bound to the bone marrow, myeloma cells multiply.
Normal plasma cells produce one of five types of antibodies or immunoglobulins -- IgG, IgA, IgM, IgE, or IgD. Each of these proteins has a slightly different function in the body. Myeloma cells also produce these immunoglobulins, but myeloma cells make them in excessive amounts. About half of myeloma patients produce very high levels of IgG, 20 percent produce high levels of IgA, and a few patients produce excessive levels of IgD or IgE. Most people with myeloma also have protein in their urine and blood, a condition called Bence-Jones proteinuria. One percent of myeloma patients have a form of the disease called nonsecretory myeloma in which there is no protein in their blood or urine, but malignant plasma cells are present in the bone marrow.
Over time, as myeloma cells divide and increase in number, they affect the patient in a number of ways. Myeloma cells interfere with the body's ability to build bone, and instead cause bones to weaken and break down -- especially those in the spine, skull, ribs, and pelvis. Eventually myeloma cells permeate the interior of the bone (the medullary cavity) and also erode the outer layer of the bone (the cortex). Minor stresses and injuries are more likely to fracture weakened bones; these are called pathologic fractures. As bones break down, calcium is released into the bloodstream, often leading to a condition called hypercalcemia, which can cause pain, nausea, vomiting, altered mental states, depression, headache, and, in severe cases, coma.
As myeloma cells take over the marrow space, they prevent bone marrow from producing essential blood cells, including red and other white blood cells. Patients with multiple myeloma are therefore prone to anemia, which is caused by low levels of red (oxygen-carrying) blood cells, and to infections because of the lack of white (infection-fighting) blood cells.
In a condition sometimes called "myeloma kidney," high levels of calcium and/or protein in the blood can interfere with the way kidneys function and diminish their ability to filter the blood properly. Over time, this can lead to permanent kidney damage and ultimately, kidney failure.
