Navigation Links
Gene profiling can single out the worst cases of multiple myeloma and guide therapy
Date:9/18/2007

ATLANTA Multiple myeloma patients vary widely in how they respond to treatment, but now researchers at the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences have identified a small subset of genes whose activity could predict high-risk cases and potentially guide therapy in the future.

Researchers followed 532 multiple myeloma patients for seven years after 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 present their data today at the American Association for Cancer Researchs second International Conference on Molecular Diagnostics in Cancer Therapeutic Development, in Atlanta, Ga.

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 lead researcher John D. Shaughnessy, Jr., Ph.D., a professor of medicine at the Myeloma Institute for Research and Therapy. If we can categorize a patients 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.

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 most often treated through the use of high dose chemotherapy and peripheral bloodderived stem cell support. While multiple myeloma often responds well to initial treatment, it often becomes drug resistant and patients are prone to relapse.

According to the researchers, survival varies greatly between low-risk and high-risk patients. At 24 months, about 90 percent of low-risk patients will be alive, whereas about 50 percent of the high-risk patients have succumbed to the disease, said Fenghuang Zhan M.D., Ph.D., of the University of Arkansas for Medical Sciences.

To understand the possible molecular mechanisms driving initiation and progression of multiple myeloma, the researchers 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.

Using purified tumor cells taken from 532 newly diagnosed patients who went on to receive uniform therapy, the researchers screened over 54,000 genes across the human genome for signs that might relate to multiple myeloma survival estimates. About 13 percent of all the patients they studied exhibited a genetic pattern that fit into the high-risk category, a frequency that rose to 76 percent among relapsed patients.

The observation of an increase in the gene expression risk score among relapsed patients provides evidence that there are likely to be small subsets of high-risk cells even in patients with low risk disease, and that current therapeutics are sub-optimal in that they kill off the low-risk cells, leaving behind cells that exhibit a high-risk genetic profile, Shaughnessy said. Currently, the researchers have experiments underway to definitively prove this concept.

Initially, the researchers identified 70 genes linked to early cancer-related death, although further analysis narrowed that number to 17. Remarkably, about 30 percent of the genes that predict high risk are found on chromosome 1, enough so that Shaughnessy recognized 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 over-produced in high-risk patients mapped to the long arm of chromosome 1, while the majority of genes that were down-regulated or suppressed mapped to the short arm of the same chromosome.

Together these data suggest that defects in chromosome 1 may be directly related to the acquisition of higher risk in patients with multiple myeloma, Shaughnessy said. Gene expression profiles have now provided us with signposts that help us risk stratify patients and tailor therapies accordingly.

Importantly, these data may provide researchers with key insights into molecular mechanisms driving disease severity which might be the target of future therapies, Shaughnessy said.


'/>"/>

Contact: Greg Lester
lester@aacr.org
267-646-0554
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. Nutrient Profiling System Launched By Food Officials in UK
2. Proteomic Profiling Can Detect Preterm Birth Risk
3. Profiling of Cancer Genes May Lead to Earlier Detection Human Cancers
4. Single gene analysis for diagnosis of a range of blood disorders
5. Single drug for bipolar disorder
6. Treating Testicular Cancer With A Single Dose Of Chemotherapy
7. Decreasing Multiple Births By Single Embryo Transfers
8. Successful creation of human embryos from a single parent for the first time
9. Skin Cancer caused by mutations in a single Gene
10. Single gene skin cancer cause
11. Drug Firms To Produce Single Pill AIDS Treatment
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... June 27, 2016 , ... ... announced today its affiliation with Tennessee Counseling Association. This new relationship ... of the Tennessee Counseling Association, adding exclusive benefits and promotional offers. , "TCA ...
(Date:6/26/2016)... N.J. (PRWEB) , ... June 27, 2016 , ... Quality ... sources, yet in many ways they remain in the eye of the beholder, according ... (EBO), a publication of The American Journal of Managed Care. For the full issue, ...
(Date:6/26/2016)... ... ... Brent Kasmer, a legally blind and certified personal trainer is helping to develop a weight ... app plans to fix the two major problems leading the fitness industry today:, ... program , They don’t eliminate all the reasons people quit their exercise program ...
(Date:6/25/2016)... Miami, FL (PRWEB) , ... June 25, 2016 , ... The temporary closing of Bruton ... Plant City Observer , brings up a new, often overlooked aspect of head lice: ... The closing for fumigation is not a common occurrence, but a necessary one in the ...
(Date:6/25/2016)... ... June 25, 2016 , ... Dr. ... from injury. Recently, he has implemented orthobiologic procedures as a method for treating ... one of the first doctors to perform the treatment. Orthobiologics are substances that ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016  Global Blood Therapeutics, ... company developing novel therapeutics for the treatment of ... announced the closing of its previously announced underwritten ... at the public offering price of $18.75 per ... were offered by GBT. GBT estimates net proceeds ...
(Date:6/24/2016)... ALEXANDRIA, Va. , June 24, 2016 ... a set of recommendations that would allow ... information (HCEI) with entities that make formulary and coverage ... determine the "value" of new medicines. The ... that does not appear on the drug label, a ...
(Date:6/24/2016)... According to a new market ... Needles, Safety Pen Needles), Needle Length (4mm, 5mm, 6mm, ... of Purchase (Retail, Non-Retail) - Trends & Global Forecasts ... market for the forecast period of 2016 to 2021. ... by 2021 from USD 1.65 Billion in 2016, growing ...
Breaking Medicine Technology: