Useful Definitions and Diagnostic Tests

Diagnostic testing for multiple myeloma utilizes unique blood, urine, and bone marrow tests in addition to a variety of standard medical tests. Cancer Connect provides comprehensive information on Blood Tests, Diagnostic Imaging techniques and the emerging field of Genomics which evaluates the genetic make-up-the DNA-of cancer cells. Tests specific to multiple myeloma include the following:

Immunoglobulin’s: Immunoglobulin’s (antibodies) are produced by multiple myeloma cells and the production of these abnormal immunoglobulin’s offer no benefit to the body and ultimately lead to the detrimental health effects suffered by myeloma patients including kidney impairment, interference with blood cell production and an impaired immune system.

Each immunoglobulin is made up of four protein chains: two long chains (called heavy chains) and two shorter chains (called light chains). Immunoglobulin’s are classified according to the heavy chain and are identified by use of a Greek letter: gamma (IgG), alpha (IgA), mu (IgM), epsilon (IgE), or delta (IgD). Normally, a plasma cell makes one of these five major classes of immunoglobulin, and each type of immunoglobulin has a slightly different function in the body. The abnormal immunoglobulin made in multiple myeloma is called the M or (monoclonal) protein.

Immunoglobulin light chains are defined by use of the Greek letters kappa or lambda. In 75% of patients, the plasma cells also produce monoclonal incomplete immunoglobulins, called light chains. These are excreted in the urine and are the so-called Bence Jones proteins. Bence Jones proteins are named after a British physician, Henry Bence Jones (1813-1873), who first discovered them. Bence Jones proteins may deposit in the kidney, clogging the tubules.  In some cases, the plasma cells may produce incomplete immunoglobulin (light chain myeloma), or they may not secrete them at all (non-secretory myeloma).

Serum protein electrophoresis (SPEP): Detects the presence and level of various proteins, including the immunoglobulin protein made by myeloma cells.  The SPEP can detect and measure the unique Monoclonal or M protein; higher levels indicate more extensive disease.

Immunofixation electrophoresis (IFE; also called immunoelectrophoresis): Identifies the type of abnormal antibody proteins in the blood.

Freelite™ serum free light chain assay: Measures antibody light chains made by myeloma cells called kappa or lambda. Abnormal levels and/or ratio suggest the presence of multiple myeloma or a related disease.

Urine protein level: (performed on a 24-hour specimen of urine) Measures the presence and level of Bence Jones proteins (otherwise known as myeloma light chains). Presence indicates multiple myeloma, and higher levels indicate more extensive disease.

Urine protein electrophoresis (UPEP): Determines the presence and levels of specific proteins in the urine, including M protein and Bence Jones protein. Presence of M protein or Bence Jones protein indicates multiple myeloma.

Beta2-microglobulin (ß2-M) level:  Determines the level of a protein in the blood that indicates the presence/extent of multiple myeloma and kidney function. Higher levels indicate more extensive disease; aids in staging of disease.

Imaging studies:  Bone [skeletal] survey, X-ray, magnetic resonance imaging,(MRI) computerized tomography(CT), positron emission tomography(PET). Assess changes in the bone structure and determine the number and size of tumors in the bone.  Higher levels of bone changes suggest the presence of multiple myeloma. 

Bone Marrow Biopsy: Determine the number and percentage of normal and cancerous plasma cells in the bone marrow. Presence of myeloma cells confirms the diagnosis. A higher percentage of myeloma cells indicate more extensive disease.

Gene: Set of coded instructions in cells for making and controlling cells.

Cytogenetics is the study of chromosomes, the long strands of bundles of coded instructions for making and controlling cells. Cytogenetics involves examining a sample of cells with a microscope to look for changes in the cells’ chromosomes. This type of test is used to detect abnormal chromosomes and measure the number of cells that have them. The pathologist will use a microscope to examine a “map” of the chromosomes, called a karyotype. The pathologist will assess the size, shape, number, arrangement, and structure of the chromosomes on the karyotype to look for any abnormal changes. Cytogenetics is used to identify the presence of DNA alterations. Certain DNA alterations may indicate how aggressive the disease is and can also be used to monitor how well treatment is working.  Cytogenetic testing can be performed on cells from the peripheral blood or bone marrow.

Fluorescence in situ hybridization (FISH) is another test used to detect the Philadelphia chromosome and the BCR-ABL fusion gene. This test may be used on a peripheral blood sample if a bone marrow sample can’t be collected. FISH uses color “probes” to find the BCR gene and the ABL gene in chromosomes. The BCR-ABL fusion gene, located on the Philadelphia chromosome, is shown by the overlapping colors of the two probes. FISH analysis of peripheral blood may be used to diagnose CML when bone marrow cytogenetics isn’t possible. But, FISH is not currently recommended for monitoring the response to treatment.

Human leukocyte antigens (HLA): special proteins on the surface of white blood cells that help the body to identify its own cells from foreign cells.

HLA type:  a unique set of HLA proteins on a person’s white blood cells. HLA types differ among people just like blood types differ among people. HLA testing is used to determine a person’s HLA type. HLA testing is done to determine the role of allogeneic stem cell transplant. It’s very important that donor and patient HLA types are a near-perfect match. The better the match, the better the outcome from treatment.

Calcium:  Hypercalcemia: Many multiple myeloma patients develop hypercalcemia, which is an increased level of calcium in the bloodstream. Hypercalcemia results from the destruction of bone from osteolytic lesions or sometimes from the development of generalized osteoporosis, in which all the bones are soft and porous and have lost calcium. Hypercalcemia in patients with multiple myeloma causes fatigue, lethargy and other symptoms. Severe hypercalcemia is a medical emergency requiring immediate treatment.

Kidney Dysfunction: In 75% of patients, the plasma cells also produce monoclonal incomplete immunoglobulins, called light chains. These are excreted in the urine and are the so-called Bence Jones proteins. Bence Jones proteins are named after a British physician, Henry Bence Jones (1813-1873), who first discovered them. Bence Jones proteins may deposit in the kidney, clogging the tubules. Ultimately, this damages the kidney and can cause renal failure. Hypercalcemia may exacerbate kidney problems because excess calcium in the bloodstream causes excessive fluid loss and dehydration. Because the abnormal proteins produced by the plasma cells are eliminated from the body through the urine, they may accumulate in the kidneys and cause kidney dysfunction. In addition to treating the underlying cancer, it is important for patients to maintain adequate oral intake of fluids to help avoid kidney failure and avoid using over-the-counter medications such as non-steroidal anti-inflammatory drugs that can worsen kidney function.