WEDNESDAY, Oct. 26, 2005 (HealthDay News) -- Every year, nearly 10,000 Americans are diagnosed with chronic lymphocytic leukemia (CLL); it's the leading type of leukemia in the United States, usually striking those over 50.
About 60 percent of patients will develop a very slow-moving form of the disease, characterized by prolonged survival and no immediate need for aggressive therapy. The remaining 40 percent of CLL patients develop a much more deadly, fast-moving malignancy requiring swift and intensive treatment.
Trouble is, doctors have had no cheap, easy and accurate means of determining which of these two disease types a patient has.
Now, a team of researchers report that a group of 13 "microRNA" genes form a kind of signature that separates "bad" CLL from the less-virulent form of the disease.
"You can make a prognosis of CLL by just looking at these microRNA," said lead researcher Dr. Carlo M. Croce, chairman of the College of Medicine and Public Health at Ohio State University.
"Already from this signature, we know whether you should leave that CLL in peace or treat it aggressively. And that's the most important thing a doctor should know," he said.
What's more, Croce said, microRNA -- tiny bits of genetic material governing gene regulation -- may also point to the underlying causes of CLL and many other cancers, and may even offer up new drug targets.
"I think this field will go very far," he said. "It's a revolutionary area."
His team published its findings in the Oct. 27 issue of The New England Journal of Medicine.
There's currently no cure for CLL, although treatments exist that can extend survival. Figuring out which patients need these therapies has always been difficult, said Croce, who is also a professor in the department of molecular virology, immunology and medical genetics at the university's Comprehensive Cancer Center.
There are two existing markers for slow-moving, indolent CLL -- low production of a protein called ZAP-70, and mutations in a gene called IgVH -- but Croce said they are "cumbersome and [relatively] inaccurate."
He explained that about three years ago his team was busy searching for a protein-producing gene that might help trigger CLL. When the researchers finally honed in on the most likely location for the gene, "there wasn't any such gene there," Crone said.
"But there were two microRNAs called mir 15 and 16," he said. "That was the first evidence ever of the involvement of a microRNA gene in human cancer."
Until very recently, scientists hadn't even known of the existence of microRNAs, which -- unlike other genes -- don't produce proteins. Instead, they interfere with other forms of RNA to help regulate gene activity. That means their activity can have "dramatic" downstream implications, according to Croce. In fact, studies have since revealed that microRNAs "are involved in all human cancers," he said.
Chang-Zheng Chen is assistant professor in the department of microbiology and immunology at the Institute for Cancer/Stem Cell Biology and Medicine at Stanford University School of Medicine. He said, "There's still a lot to be learned about how microRNA works, and what the implications are for biology."
According to Chen, "the excitement is that this is a new paradigm of gene regulation which will give us a new opportunity to find things out about cancer that we didn't already know."
One of those discoveries may already be at hand. In its study, Croce's team analyzed microRNA expression patterns in 94 different cancer cell lines taken from patients with CLL. They also examined 42 candidate microRNA genes, looking for cancer-linked abnormalities.
They discovered that a grouping of 13 microRNA formed a distinct genetic "signature" separating slow-moving CLL from the more deadly form of the disease.
Croce is hopeful this gene test might someday become routine for newly diagnosed CLL patients. "Not only is this method practical, it's simple and cheap," he said. "Instead of looking at 30,000 genes you're looking at just 13."
MicroRNA may someday prove useful in the treatment of CLL and other cancers, too, he said. "MicroRNA themselves can actually be a drug, because they are so small and can get into the [cancer] cell," Croce explained. "In fact, mir 15 and 16 cause apoptosis -- programmed cancer cell death."
"We can also do a lot of pharmacogenetics, to see how alterations in microRNA affect sensitivity to drugs, and also determine how drugs affect the expression of microRNA. We know nothing about that right now, that's an area we're only starting to explore," he said.
Croce said his team is currently investigating the role of microRNA in CLL and a host of other cancers, including solid tumors. "In every tumor type we look at we see alteration of microRNA genes," he noted.
But Chen, the author of a related commentary in the journal, stressed that this line of research is in its infancy.
"I'm hopeful, but this is still at the very early stage" he said. "Is this going to be the magic bullet for cancer diagnosis and treatment? I do think there are opportunities here -- but it's still early days."
More information
Learn more about CLL from the Leukemia & Lymphoma Society.
