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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?

Myeloma cellsMultiple myeloma is a cancer of 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 the immune system is exposed to disease-causing bacteria and viruses (pathogens), some B cells become plasma cells and begin to produce antibodies. Plasma cells can be seen in bone marrow, lymphoid tissues (such as lymph nodes), and the respiratory tract, usually in low numbers. Photo source: NCI, Lydia Kibiuk

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). Depending on the number of tumors, this condition has different names:

  • Plasmacytoma—a single plasma cell tumor forms in the bone or elsewhere in the body
  • Multiple myeloma—more than one plasma cell tumor forms in the bone

Since the malignant cells are clones, derived from a single plasma cell, they all produce identical antibodies called abnormal Monoclonal immunoglobulins (M proteins), which are present in the blood and sometimes in the urine.

Normally, the body makes five different types of immunoglobulins – IgG, IgM, IgA, IgE and IgD. Each one has 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 molecule. 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 and/or produce an excess of only one of the light chains, or rarely heavy chain-only types. These identical immunoglobulins or light chains are also known as Monoclonal proteins or M proteins. 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.

  • Intact immunoglobulin—people are most likely to have IgG and IgA myelomas, with IgG types making up about 60% of myelomas and IgA types making up about 20% of myelomas. Cases of IgE and IgD are rarely reported. Some people who produce monoclonal IgM may have a related but different condition called Waldenström macroglobulinemia. (For more on this, see the American Cancer Society's webpage on this disorder and the International Waldenstrom's Macroglobulinemia Foundation site.)
  • Light chain—myeloma patients producing an abnormal amount of only light chains are in the minority. They comprise about 20% of cases. The M-proteins that they produce are called free light chains (Bence Jones) proteins. Surplus free light chains are released into the bloodstream and since they are relatively small molecules, they are filtered by the kidneys and released into the urine. Free light chains are typically found in small quantities in the blood and large quantities in the urine.

Risks
Multiple myeloma is relatively uncommon and comprises about 1% of cancers. The American Cancer Society estimates that about 30,000 new cases of multiple myeloma are diagnosed each year in the U.S. and that 12,500 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 at least 65 years old. 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 signs, 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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