Cancer's Musical Chairs

Multiple myeloma more aggressive with chromosomal translocation

(RxWiki News) A lot of medical research may not prove beneficial to patients right away, but all research advances the disease knowledge base. Such is the case with a new study relating to multiple myeloma, a rare blood cancer.

A genetic abnormality has been found that dims the overall outlook of people with multiple myeloma, an incurable cancer of the blood plasma cells in the bone marrow.

Researchers at Washington University School of Medicine in St. Louis found that two chromosomes switch places in what's technically called "translocation" in more serious cases of multiple myeloma. 

"Annual blood work may be good for you; ask your doctor."

“Even in this cancer that has no cure, patients with the 4, 14 translocation tend to do very poorly with treatment,” says Michael H. Tomasson, MD, associate professor of medicine. “But no one really knew why.”

One in five multiple myeloma patients has the translocation. When this defect shows up, the cancer is resistant to chemotherapy, and patients don't usually live as long as people without this rearrangement.

A specific gene that directs the way DNA is packaged - WHSC1 - also gets off track. This is not good because the gene makes proteins that determine when cells turn on and off. And cancer results from haywire cell growth.

To learn more, researchers took a closer look at the area of the gene that codes for proteins. They found the missing piece was located in what's called the non-coding region of the gene.

That exploration found an RNA (controls cell processes) called ACA11 that's seen in quite high levels in people with multiple myeloma who have the chromosomal translocation.

Digging deeper, the scientists learned that as levels of ACA11 go up, the cancer cells were protected from the effects of the chemotherapy. And experiments showed just the opposite occurred as well.

“ACA11 appears to protect the cancer cells from damaging stress,” Dr. Tomasson said. “It allows the cells to grow better and be resistant to chemotherapy."

"And if you look at multiple myeloma patients with the 4, 14 translocation, they tend to show resistance to treatment as well. Not to every chemotherapy, but they show resistance to a number of them,” said Dr. Tomasson.

Interestingly, ACA11 is present in other malignancies, including brain, bladder, esophageal and colon cancers, according to Dr. Tomasson. So these findings may go beyond understanding multiple myeloma better.

"We can look for drugs that attack this mechanism,” he said. “We don’t yet have these drugs or other answers to know what will work well for these patients. But this is an important clue that tells us where to look.”

Findings from this research were published July 2 in the Journal of Clinical Investigation.

The research was funded by the Multiple Myeloma Research Foundation, the Barnes-Jewish Hospital Foundation, a NMRC Clinician Scientist Award and Harvey and Linda Saligman. No conflicts of interest were reported.

Review Date: 
July 7, 2012