New test identifies B-cell tumor markers

July 29, 2002

Orlando, FL - In the United States, multiple myeloma accounts for about one percent of all cancers, and approximately 12,500 new cases are diagnosed every year. This uncommon cancer affects men and women equally, and is usually seen in people over 40 years old. Its cause is unknown. Current methods for identifying and monitoring patients' B-cell lineage tumors such as myoloma rely on electrophoresis-based testing for Bence-Jones (BJ) proteins, which are homogeneous populations of k or l free light chain (FLC) molecules produced by malignant B-cell clones. This type of testing, usually performed on urine specimens, is expensive, time-consuming and sometimes inaccurate.

An alternative approach is immunoassay measurement of FLC concentrations in serum. Immunoassay analyzers are common tools in the hospital laboratory, and studies show that increased urine concentrations of k or l FLC molecules correlate well with increased serum concentrations of the same FLC, and that serum testing may be diagnostically more accurate if patients have renal failure. However, immunoassays must be highly specific because serum concentrations of FLCs are several orders of magnitude lower than those of light chains found in urine, which are bound to intact immunoglobulins.

A novel immunoassay for FLC molecules was described last year in an article titled "Highly Sensitive, Automated Immunoassay for Immunoglobulin Free Light Chains in Serum and Urine," which appeared in the scientific journal Clinical Chemistry. This week, at the 54th Annual Meeting of the American Association for Clinical Chemistry (AACC), lead author Arthur Bradwell, MD, from The Medical School at Edgbaston, Birmingham, U.K., and the Binding Site, also in Birmingham, will update the findings from his group's investigation.

AACC (http://www.aacc.org/) is the scientific organization for clinical laboratory professionals, physicians, and research scientists. Their primary commitment is the understanding of laboratory testing to identify, monitor and treat human disease. More than 11,000 attendees are expected for the meeting, which is being held at the Orange County Convention Center, Orlando, Fla., July 28-August 1, 2002.

Background
Multiple myeloma is a plasma cell cancer in which a clone of abnormal plasma cells multiplies, forms tumors in the bone marrow, and produces a large quantity of abnormal antibodies that accumulate in the blood or urine. Plasma cell tumors (plasmacytomas) are most common in the pelvic bones, spine, ribs, and skull, and they occasionally develop in other areas. The abnormal plasma cells almost always produce a large quantity of abnormal antibodies, and the production of normal antibodies is reduced. Deposits of antibody pieces in the kidneys or other organs can also lead to amyloidosis, another serious disorder.

Multiple myelomas are the result of tissue infiltration by plasma cells and are characterized by multiple tumorous masses of neoplastic plasma cells throughout the skeletal system. There is increased osteoclastic activity resulting from cytokines that increase bone resorption in areas infiltrated by plasma cells. The consequences of the infiltrated tissues can be found in the bone (pain, pathologic fractures, lytic lesions, hypercalcemia), bone marrow (anemia, leukopenia, thrombocytopenia), kidneys (renal failure), as well as lymph nodes, liver and spleen.

Early serum immunoassays involved separating FLCs from intact immunoglobulins before analysis, and although accurate, they were impractical for routine use. Subsequent assays have used antibodies directed against "hidden" epitopes of FLC molecules that are located at the interface between the light and heavy chains of intact immunoglobulins. The use of monoclonal antibodies appears to be an obvious approach to improving specificity, but such antibodies have been difficult to develop and their use has been restricted to radioimmunoassay and enzyme immunoassays, which are more complicated than turbidimetric techniques and therefore not ideal for routine use in immunochemistry laboratories.

The study by Bradwell, et al. describes the development and assessment of a sensitive, latex-enhanced, turbidimetric, FLC assay for use on a popular automated immunoassay system. In his presentation at the AACC Annual Meeting, Bradwell will compare detection limit of this new assay with those of existing clinical laboratory tests for FLCs, discuss its potential in the clinical laboratory and review the following issues:
-end-
Editor's Note: To schedule an interview with one of the researchers, please contact Donna Krupa at 703.527.7357 (direct dial), 703.967.2751 (cell) or djkrupa1@aol.com. Or contact the AACC Newsroom at: 407.685.4215.

American Association for Clinical Chemistry

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