Gene Profiling Predicts High-Risk Cases of Multiple Myeloma

A small subset of genes has been identified whose activity could predict high-risk multiple myeloma cases and guide therapy in the future.

Multiple myeloma is a cancer affecting the blood plasma cells in bone marrow that produce antibodies. Nearly 14,600 new cases of multiple myeloma occur each year in the United States. The disease is generally treated by high-dose chemotherapy and peripheral blood-derived stem cell support. Multiple myeloma often responds well to initial treatment, but it frequently becomes drug resistant and patients are prone to relapse.

To understand the possible molecular mechanisms driving initiation and progression of multiple myeloma, scientists launched a large-scale, longitudinal study to categorize the differences in gene expression patterns, that is, which genes are activated and inactivated in relatively indolent versus aggressive disease.

Investigators from the University of Arkansas School for Medical Sciences (Little Rock, AR, USA) followed 532 multiple myeloma patients for seven years after a blood stem cell transplant to create a genetic profile to chart the severity of the disease. The team determined that the activity of as few as 17 genes could mean the difference between high or low risk for a poor prognosis. They presented their data at the American Association for Cancer Research's second International Conference on Molecular Diagnostics in Cancer Therapeutic Development (Atlanta, GA, USA) in September 2007.

About 30% of the genes that predict high risk are found on chromosome 1, enough to suggest a trend among the genes, based on where they map on each chromosome in the human genome. The majority of genes that were up-regulated--or overproduced--in high-risk patients mapped to the long arm of chromosome 1, while the majority of genes that were downregulated--or suppressed--mapped to the short arm of the same chromosome.

"There are enormous differences between how different people fare with multiple myeloma. While most do very well others have a highly aggressive form of the disease and this is not recognized well with current prognostic variables,” said Prof. John D. Shaughnessy, Jr., Ph.D., from the Myeloma Institute for Research and Therapy at the University of Arkansas School for Medical Sciences (Little Rock, AR, USA). "If we can categorize a patient's risk early, we can better guide that patient toward therapies that might be more effective for them based on the genetic profile of the disease.”


Related Links:
University of Arkansas School for Medical Sciences
Myeloma Institute for Research and Therapy at the University of Arkansas School for Medical Sciences