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Multiple Myeloma

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Also known as: Plasma Cell Myeloma; Plasma Cell Dyscrasia; Plasmacytoma; Plasmacytoma of Bone; Plasma Cell Neoplasm; Extraosseous Plasmacytoma

What is multiple myeloma?

Multiple myeloma is a cancer of the plasma cells. Plasma cells develop from one type of white blood cell called B lymphocytes and are an important part of the immune system. Their primary function is to produce antibodies – targeted immunoglobulin proteins that help protect the body against infections. Normally, plasma cells are produced as needed. When B cells are exposed to disease-causing bacteria and viruses (pathogens), some of them become plasma cells and begin to produce antibodies. Plasma cells can be seen in bone marrow, lymphoid tissues (e.g., lymph nodes), and the respiratory tract, usually in low numbers.

Sometimes, however, a plasma cell may become malignant. It begins to divide uncontrollably, generating numerous copies of itself (clones) that form tumors in the bone marrow and crowd out other types of normal cells. In time, these tumors interfere with normal cell production and erode the surrounding bone, producing soft spots and holes (lytic lesions). Since the malignant cells are clones, derived from a single plasma cell, they all produce identical antibodies, abnormal monoclonal immunoglobulins (M-proteins), that are released into the blood and sometimes excreted in the urine.

Normally, the body makes five different types of immunoglobulins – IgG, IgM, IgA, IgE and IgD – that have slightly different immune system functions. Each type of immunoglobulin is composed of four protein chains – two identical heavy (long) protein chains and two identical light (shorter) protein chains. The heavy chains may consist of one of five different types that correspond with the type of immunoglobulin produced: gamma (IgG), mu (IgM), alpha (IgA), epsilon (IgE) and delta (IgD). The light chains consist of one of two different types called kappa and lambda. Within a plasma cell, two heavy chains of one type and two light chains of one type become attached to form one intact immunoglobulin. Each particular plasma cell will produce only one type of immunoglobulin.

In people with multiple myeloma, the malignant plasma cells produce only one type of intact (whole) immunoglobulin in large amounts or produce an excess of only one of the light chains, or rarely heavy chain types. These identical immunoglobulins or light chains are also known as monoclonal proteins or M proteins. Myeloma patients producing an abnormal amount of only light chains are in the minority; the M-proteins that they produce are referred to as free light chains or Bence Jones proteins. The surplus free light chains are released into the bloodstream and, because they are relatively small molecules, they are filtered by the kidneys and excreted into the urine. Bence Jones proteins are typically found in small quantities in the blood and large quantities in the urine. Though the type of M protein produced by malignant cells may vary from one person to the next, within one particular person it is always the same since it is produced by identical or cloned plasma cells.

The type of myeloma a person has is often referred to by the type of M protein produced, whether an intact immunoglobulin or light chain. People with IgG and IgA myelomas are the most common, with IgG types comprising about 50-60% of myelomas, IgA types making up about 20% of myelomas, and light chain only about 20%. Cases of IgE and IgD are rarely reported. Some people who produce monoclonal IgM may have a related but different condition called Waldenstrom macroglobulinemia. (For more on this, see the American Cancer Society's webpage on this disorder.)

Multiple myeloma is relatively uncommon and comprises about 1% of cancers. The American Cancer Society estimates that about 22,000 new cases of multiple myeloma are diagnosed each year in the U.S. and that a little over 10,000 people with multiple myeloma die. The cause of multiple myeloma is not yet known. The risk of developing it increases with age, with the majority of cases being diagnosed in people 60 years or older. While there are a few families who have a higher incidence of multiple myeloma, most people will not have any affected relatives. It is thought that the disease may be associated with a decrease in immune system function, occupational exposure to toxins and/or solvents, genetic factors, certain viruses, and radiation exposure.

 Monoclonal Gammopathy of Undetermined Significance (MGUS)
Sometimes people will produce small amounts of identical copies of the same immunoglobulin (also known as monoclonal gammopathy) but not have any of the symptoms or complications of multiple myeloma. This condition is referred to as monoclonal gammopathy of undetermined significance or MGUS. Often, this condition is only discovered when routine tests reveal abnormal amounts of protein in the blood. About 1% of these people per year progress to multiple myeloma or some other related disease, such as lymphoma. Generally, these people do not require any treatment, but they are closely monitored. Some of the tests used to diagnose and/or follow multiple myeloma are used to monitor people with MGUS.

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