WEDNESDAY, Aug. 25, 2004 (HealthDayNews) -- A new test for a genetic marker will give some people with chronic lymphocytic leukemia (CLL) peace of mind, but at the same time will let others know they may need to start treatment for their cancer.
In a study in the Aug. 26 issue of the New England Journal of Medicine, researchers report that ZAP-70 is a protein expressed mainly in people with the more aggressive form of CLL.
"We need to improve how we treat this disease and identify early on which patients may get into trouble, and give them the option of looking at new treatment options," said the study's lead author, Dr. Thomas Kipps, deputy director of research at the Moores University of California, San Diego, Cancer Center.
"This study validates that ZAP-70 is a useful marker, and it helps to highlight who may need treatment," said Kipps.
Chronic lymphocytic leukemia is a relatively rare disease, affecting about 8,200 Americans each year, according to the National Cancer Institute. The disease occurs most often in middle-aged and elderly individuals. Nearly 5,000 people die each year from the disease.
CLL comes in two forms, according to Dr. Terry Hamblin, a professor of immunohematology at the University of Southampton, U.K., and author of an accompanying editorial in the same issue of the journal. One form had an average life expectancy of about eight years and was universally fatal. The other form had an average survival of 25 years, and Hamblin said most people with this form die of other causes rather than of their cancer.
Kipps said the problem is if you treat everyone with CLL, those who have the slowly progressing form of the disease may actually end up sicker than if they hadn't been treated. So, the current treatment protocol is to watch and wait, with no treatment given until disease symptoms become evident. But Kipps says that, for people with more aggressive disease, it may be that earlier treatment would be more effective.
So, researchers have been analyzing the DNA of CLL to help separate those who have the more severe course of the disease from those who may never need treatment.
Hamblin discovered a way to analyze the DNA of people with CLL. He discovered that if specific mutations were present, overall patient prognosis was good. However, this test was expensive and time-consuming, so not all labs could easily perform it.
Then, Hamblin said, researchers from the National Institutes of Health spotted varieties in about 200 genes that distinguished the two forms of the disease. ZAP-70 was the one that showed the greatest variance, he said. It was present in unmutated cancer cells but absent in mutated cells.
Several groups of researchers then went to work to create a less expensive way of detecting ZAP-70. According to Hamblin, three groups of researchers, including Kipps', have come up with similar tests that likely can be performed in most labs.
Kipps points out, however, "that it's not a perfect world. There are patients expressing unmutated genes that don't express ZAP-70, and conversely, some people have mutated genes that express ZAP-70."
What's most important, Kipps said, is the level of ZAP-70. Kipps explained that the researchers working on this project had a pair of 57-year-old twins who both had CLL. Both had mutated cancer cells, but one had cancer cells that expressed ZAP-70. That twin had the more severe form of the disease, said Kipps.
"That gave us a clue to look more closely at ZAP-70 levels. When the test is below a certain level of ZAP-70, patients appear to have a [less severe] course," said Kipps.
In looking at B cells from 307 people with CLL, Kipps said they found ZAP-70 was expressed above the threshold level in 117 of 164 people with the unmutated gene, and in 24 of 143 people with a mutated gene.
The average time before having to begin treatment was 2.8 years for those with an unmutated gene and 4.2 years for those with both a mutated gene and high levels of ZAP-70. For those without high levels of ZAP-70, the average time before treatment was 7.1 years for those with an unmutated gene and 11 years for those with a mutated gene.
Besides signaling who may need treatment and who shouldn't receive therapy, Kipps said, ZAP-70 may also provide important clues for developing new treatments.
"Were learning more about the leukemia cell and what helps it survive and progress. We'd like to see how we can interfere with its expression, and maybe we can actually offset the tendency for trouble," said Kipps.
More information
To learn more about chronic lymphocytic leukemia, visit the National Cancer Institute.
