Researchers recently announced that the blood disorder monoclonal gammopathy of undetermined significance (MGUS) precedes the vast majority of multiple myeloma diagnoses. Until now, researchers had disagreed whether MGUS was a consistent precursor to full-blown myeloma disease.

Study authors examined blood samples from 71 people who developed multiple myeloma while enrolled in the National Cancer Institute's Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Since its inception in 1992, the trial had collected frequent blood samples from participants, making it an invaluable resource for investigating early cancer markers. Although the trial did not aim to investigate multiple myeloma specifically, its database contained the 71 multiple myeloma patients' blood samples from years before they became sick.

In analyzing these samples, researchers discovered that almost every patient's blood showed evidence of preceding MGUS. In some cases it appeared as early as a decade before the multiple myeloma diagnosis. While the vast majority of MGUS cases do not progress to multiple myeloma, these findings confirm what many physicians, like Dr. Robert A. Kyle of the Mayo Clinic, have long suspected, "MGUS is a precursor lesion of multiple myeloma, and that all patients with [multiple myeloma] have a preceding MGUS or smoldering myeloma."

MGUS is an asymptomatic blood disorder characterized by an abnormally elevated level of monoclonal protein, often discovered incidentally during testing for other disorders. Monoclonal proteins, or "M-proteins," are produced by plasma cells in the bone marrow. The presence of M-protein in the blood indicates that these plasma cells are proliferating excessively, similar to what occurs in multiple myeloma. Unlike full-blown cancer, even elevated M-protein levels remain relatively low in MGUS, and the disorder causes no symptoms.

Three percent of Americans over age 50 possess MGUS, and reports suggest that the condition occurs more frequently in people of African descent.

While this study confirms that MGUS precedes virtually all multiple myelomas, researchers caution that most incidences of MGUS will never advance to clinical disease; given that only one percent of MGUS cases progress to multiple myeloma each year and that the disorder causes no ill effects, MGUS does not presently warrant treatment. "We now have a window of time for studying how multiple myeloma begins and progresses," explains lead study author Dr. Ola Landgren of the National Cancer Institute.

Past studies have already identified some risk factors for MGUS progression to multiple myeloma, including a high serum M-protein level. Further studies will hopefully clarify and identify further risk factors, as well as discover potential avenues for preventing MGUS progression. According to Kyle, multiple myeloma could essentially be wiped out if we could figure out how to treat MGUS.

For more information, see the National Cancer Institute ^[1] News Bulletin and the full study in Blood Journal ^[2]. Further information can be found in a recent Myeloma Beacon ^[3] article about the effect of radiation exposure on MGUS progression.