Multiple Myeloma

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Overview

Myeloma is a cancer that develops in cells of the bone marrow called plasma cells. Plasma cells develop from 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 pathogens, they mature into plasma cells and begin to produce antibodies. They share space in the bone marrow with maturing red blood cells (RBCs), platelets, and several types of white blood cells (WBCs). Sometimes, however, a plasma cell may become malignant and begins to divide uncontrollably, forming tumours in the bone marrow, eroding the surrounding bone and producing producing soft spots and holes known as lytic lesions. Myeloma can develop wherever there is bone marrow, including the pelvis, spine and ribcage. As it can occur in several places in the body, it is often called multiple myeloma.

Since the malignant cells are derived from a single plasma cell, they all produce an identical antibody – an abnormal monoclonal immunoglobulin (also termed an M-protein) that is released into the blood and sometimes excreted in the urine. The abnormal antibody does not work properly and is not able to fight infections while the proliferation of malignant cells can affect the production of normal antibodies (immunosuppression), causing susceptibility to infection.

Normally, the body makes five different types of immunoglobulins - IgG, IgA, IgM, 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 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 patients with multiple myeloma, the malignant plasma cells produce only one type of intact (whole) immunoglobulin in large amounts. However, in about 75% of myeloma patients, the balance in production of light and heavy chains is disturbed and light chains are produced in excess. 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, as a protein known as Bence-Jones protein. Rarely, the monoclonal protein produced consists only of light chains or, very rarely, heavy chains. Though the type of M protein produced by malignant cells may vary from one patient to the next, within one particular patient it is always the same since it is produced by identical or cloned plasma cells.

The type of myeloma a patient has is often referred to by the type of M protein produced, whether an intact immunoglobulin or light chain. Patients with IgG and IgA myelomas are the most common, with IgG types comprising about 60-70% of myelomas and IgA types making up about 20% of myelomas. Cases of IgE and IgD are only rarely reported. Some patients who produce monoclonal IgM may have a related but different condition called Waldenstrom‘s macroglobulinaaemia.

Monoclonal Gammopathy of Undetermined Significance (MGUS):
Sometimes people will produce abnormal 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 20 to 30% of individuals with will go on to develop myeloma or some other related disease such as lymphoma. Generally, these patients 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 patients with MGUS.

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