What Is Multiple Myeloma?

Multiple myeloma is a cancer of the bone marrow plasma cells, white blood cells that make antibodies. A cancerous or malignant plasma cell is called a myeloma cell. Myeloma is called “multiple” because there are frequently multiple patches or areas in bone where it grows. It can appear as both a tumor and/or an area of bone loss, and it affects the places where bone marrow is active in an adult: the hollow area within the bones of the spine, skull, pelvis, rib cage, and the areas around the shoulders and hips.

In-depth description of multiple myeloma

Myeloma is a cancer of the plasma cells in the bone marrow. Myeloma is synonymous with “multiple myeloma” and “plasma cell myeloma.” The malignant plasma cells, or myeloma cells, accumulate in the bone marrow. The major features of myeloma result from the abnormal accumulation of myeloma cells within the bone marrow, causing: 

  • — Disruption of normal bone marrow function reflected by anemia and/or low white counts or platelet counts;
  • — Destruction and invasion of bone and surrounding areas of bone marrow involvement;
  • — Production and release of monoclonal protein from the myeloma cells into the blood stream and/or into the urine;
  • — Reduction of normal immune function, reflected by reduced levels of normal immunoglobulins and increased susceptibility to infection. Infection is also more likely if the white blood cell count is low. 

Plasmacytomas are localized tumors composed of plasma cells, which can grow inside bone (intramedullary) or outside bone (extramedullary or soft-tissue). When there are multiple plasmacytomas inside or outside bone, this condition is also called multiple myeloma. When patients with myeloma have disease outside the bone marrow, this is called “extramedullary disease” (EMD).

Production of monoclonal protein by Myeloma Cells

The characteristic property of myeloma cells is the production and secretion (release) of monoclonal protein into the blood and/or urine. The amount of monoclonal protein produced by myeloma cells varies considerably from patient to patient. In assessing myeloma, it is very important to know if a patient’s myeloma cells are high producers or low producers or non-secretors (with no protein released into the blood or urine). Once the relationship between the protein level and the amount of myeloma in the bone marrow is known, it is possible to interpret and understand the relationship between a particular protein level and the myeloma tumor burden. Monoclonal protein is also called M-protein, M-component, myeloma protein, paraprotein, protein spike, or M-spike. The monoclonal protein is called a spike because of the way it appears on protein electrophoresis, a laboratory technique used to separate and identify proteins.

The monoclonal protein is an immunoglobulin or a component/fragment of an immunoglobulin. The figure on the right illustrates the structure of a normal immunoglobulin molecule. In myeloma cells, mutations have occurred in the genes responsible for immunoglobulin production. Myeloma proteins therefore have an abnormal amino acid sequence and protein structure. Typically, the normal antibody function of the immunoglobulin is lost, and the three-dimensional structure of the molecule may be abnormal.

Increased production of abnormal immunoglobulin has a number of consequences:

  • —Excess monoclonal protein accumulates in the bloodstream and/or is excreted in the urine.
  • The abnormal monoclonal molecules can adhere to each other and/or to other tissues such as blood cells, blood vessel walls, and other blood components. This can reduce blood flow and circulation, causing hyperviscosity syndrome.
  • More light chains are produced than are needed to combine with the heavy chains to create a whole immunoglobulin molecule. These excess light chains are called Bence Jones proteins (see “Annotated history” section). Free Bence Jones proteins have a molecular weight of 22,000 daltons and are small enough to pass freely into the urine.
  • The abnormal monoclonal proteins can also have a wide range of other properties including:
    • Binding to normal blood clotting factors, resulting in increased bleeding tendency, enhanced blood clotting, or phlebitis (inflammation of the veins);
    • Binding to nerves to cause neuropathy or to circulating hormones to cause metabolic dysfunction.
  •  Free Bence Jones proteins can also adhere to each other and/or to other tissue (just as the whole immunoglobulin molecule can). In this case the end result is either:
    • AL Amyloidosis – Disease in which the Bence Jones light chains (usually lambda) are cross-linked in a highly symmetric “beta-pleated” fashion and become deposited in tissue around the body, including, for example, kidney, nerves, and heart tissue; or
    • Light Chain Deposition Disease (LCDD) – Light chains (usually kappa) are deposited in a more haphazard fashion, but most selectively in small blood vessels of the eyes and kidneys; or
    • Monoclonal Immunoglobulin Deposition Disease (MIDD) – Disease in which there is deposition of fragments of heavy chains, light chains, or both heavy and light chains.

It is important to be aware that routine blood testing can give very strange results because of “stickiness” or hyperviscosity of myeloma blood samples in automated chemical analyzers and/or interference with chemical reactions.

Definitions of MGUS and myeloma

Monoclonal Gammopathy of Undetermined Significance (MGUS)
  • Monoclonal protein present but usually ‹ 3.0 g/dL
  • No CRAB features or other indicators of active myeloma
  • Bone marrow monoclonal plasma cells ‹ 10%
Asymptomatic or Smoldering Multiple Myeloma (SMM)
  • Higher level of disease than MGUS: serum M-component can be › 3.0 g/dL and/or bone marrow plasma cells › 10%, but
  • No CRAB features or other indicators of active myeloma
Active or Symptomatic Myeloma
  • Monoclonal protein present, and
  • One or more “ CRAB ” features and/or indicators of organ damage*

*Organ damage classified as "CRAB" or any other significant clinical problem linked to myeloma progression such as recurrent infections or neoropathy unrelated to treatment

C - Calcium elevation (>10mg/dL)
R - renal dysfunction (creatinine >2mg/dl or creatinine clearance (<40ml/min)
A - anemia (hemoglobin <10g/dL or >2g/dL decrease from patient's normal)
B - bone disease (one or more oteolytic lesions detected on skeletal radiography, WBLC CT or PET/CT)

One or more "CRAB" features or other significant problem required for diagnosis of Symptomatic Myeloma

New Definitions of Myeloma and Early Myeloma

Signs and symptoms of multiple myeloma


  • Persistent or worsening tiredness due to anemia or reduced kidney function
  • Sudden pain due to a broken bone in the spine, ribs, or elsewhere
  • Recurrent unexplained infections, such as pneumonia, sinus, or urinary infection


  • Pain with movement and/or at night/rest
  • Pain tenderness/swelling of bone areas
  • Swelling, shortness of breath or evidence of heart or kidney failure [late stages of the disease

Causes of myeloma

Multiple myeloma can be caused or triggered by several factors. As a result, pre-myeloma cell populations in the bone marrow that are already abnormal or damaged may be affected. Some triggers of myeloma include the following:

Exposure to toxic chemicals

The following toxic chemicals have been linked to causes of myeloma:

  • benzene
  • dioxins (such as Agent Orange)
  • certain agricultural chemicals
  • certain solvents
  • some fuels
  • engine exhaust
  • some cleaning products

Exposure to atomic radiation

Even though serious radiation exposure is rare, it has occurred in Japan and at atomic testing and reactor sites, as well as at manufacturing facilities.

Infection with cancer-causing viruses

Viruses linked to causes of multiple myeloma include the following:

  • HIV (Human Immunodeficiency Virus)
  • Hepatitis virus
  • Several herpes viruses
  • Some retroviruses, i.e. SV40 (Simian Virus 40)

Family tendency for myeloma

There is some family tendency to develop myeloma—approximately 3%–5% of myeloma diagnoses occur in a family member who has a close relative with a previous diagnosis of MGUS or myeloma. If you have a family member with myeloma, screening/early testing for MGUS can be discussed with your physician.

Immune system suppression

Multiple myeloma may also develop as a result of immune system suppression that could be caused by any number of factors.