About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Gene Mutation Responsible for Most Cases of Waldenstrom's Macroglobulinemia Identified

by Sheela Philomena on December 13, 2011 at 2:07 PM
Font : A-A+

 Gene Mutation Responsible for Most Cases of Waldenstrom's Macroglobulinemia Identified

Genetic mutation that underlies the vast majority of cases of Waldenstrom's macroglobulinemia (rare form of lymphoma) has been discovered by Dana-Farber Cancer Institute researchers.

The research (abstracts 261, 300, 434 and 597), to be presented at the American Society of Hematology's 2011 annual meeting on Monday, Dec. 12 at 2:45 p.m. PST, points to an error in a single digit of DNA --Ž one of three billion letters in the human genetic code -- Žas the leading culprit in Waldenstrom's, and a prime target for new therapies against the disease.

Advertisement

The discovery was made by sequencing the genome of tumor cells in Waldenstrom's patients, Ž reading the cells' DNA letter by letter, Ž and seeing where it differed from that of the patients' normal cells.

"We found that tumor cells in 90 percent of the patients we tested contained a single point mutation, an error in one of the bases that make up the 'rungs' of the DNA helix," says Steven Treon, MD, PhD, who led the research with his Dana-Farber colleague Zachary Hunter. "In subsequent experiments, when we treated the tumor cells with drugs that target the pathway activated by the mutated gene, the cells underwent apoptosis, or programmed cell death. These results suggest that new, effective treatments that target the tumor cells directly are now possible for people with the disease."
Advertisement

Waldenstrom's macroglobulinemia is a slow-growing form of non-Hodgkin lymphoma that originates in white blood cells known as B lymphocytes. When abnormal B cells begin to multiply out of control, they produce excessive amounts of a protein called monoclonal immunoglobulin, which causes the blood to thicken and flow less smoothly. In some patients, the disease produces no major symptoms; in others, problems can include weakness, fatigue, excessive bleeding, and weight loss. In severe cases, vision and neurological problems can occur. Approximately 2,000 to 3,000 people are diagnosed with Waldenstrom's each year in the United States; it is more common in men than women, more prevalent in people of Ashkenazi (Eastern European Jewish) descent, and arises more often in older people than young.

Although there isn't a cure for Waldenstrom's, treatments include drugs such as rituximab, bortezamib, and bendamustine. High-dose chemotherapy with autologous stem cell transplantation is infrequently also used. Since the disease was first described 70 years ago, all previous efforts to track down a genetic cause have been fruitless, Treon remarks. For the current research, Treon and his colleagues conducted whole genome sequencing of tumor cells and normal cells from 30 patients with Waldenstrom's. In collaboration with Complete Genomics of Mountain View, Calif., researchers "lined up" the sequences of the tumor and non-tumor cells to identify differences. Ninety percent of the tumor cells had a point mutation in the gene MYD88.

"The mutation causes the cells to produce a distorted protein, which switches on the IRAK complex pathway, leading to activation of NF-kB, a protein that is essential for the growth and survival of Waldenstrom's tumor cells," Treon comments. "When we shut down the pathway by blocking the abnormal protein with drug molecules, the tumor cells entered apoptosis." Equally important, the tested molecules had no adverse effect on normal cells.

The discovery of a genetic signature for Waldenstrom's will enable doctors to definitively determine which patients have the disease and not a similar condition such as other forms of lymphoma or multiple myeloma, Treon says. Drugs that block the abnormal protein or other proteins in the NF-kB pathway could, theoretically, short-circuit the disease process in many patients. Some of these drugs already exist, having been developed for other conditions. Treon and his colleagues are currently working to develop others and are testing them in experimental models.

Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Advertisement
News Category
What's New on Medindia
Fermented Skin Care
Television Binge-Watching May Boost the Risk of Deadly Blood Clots
Western Diet may Augment the Risk of Autoimmune Diseases
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
DNA Finger Printing Cystic Fibrosis McArdle Disease Inherited Breast Cancer Syndromes Von Hippel-Lindau Disease / Rare Genetic Disorder How Do Viruses Mutate and Why Does it Matter? 

Recommended Reading
Hodgkins Lymphoma
Hodgkins lymphoma or Hodgkins disease has the distinction of being the first cancer to be cured by ....
Non-Hodgkins Lymphoma
Non Hodgkins Lymphoma is a cancer that affects the lymph tissues. It is made up of a wide array of ....
Quiz on Cancer
Cancer, is the second most leading cause of death worldwide. Cancer is not just one disease but ......
Cancer Prevention thro' Lifestyle Changes
Did u know that simple changes in lifestyle could lower your cancer risks? Find out how!...
Cystic Fibrosis
Cystic fibrosis is a genetic disease involving the mucus and sweat glands and the medical world has ...
DNA Finger Printing
DNA fingerprinting is a technique which helps forensic scientists and legal experts solve crimes, id...
How Do Viruses Mutate and Why Does it Matter?
Mutations are the sudden changes that occur in genetic materials. They occur as a part of evolution ...
Inherited Breast Cancer Syndromes
Inherited breast cancers are caused due to mutations in genes that increase the risk of breast cance...
McArdle Disease
McArdle disease is a genetic disorder in which the body cannot breakdown glycogen in the muscles. It...
Von Hippel-Lindau Disease / Rare Genetic Disorder
Von Hippel-Lindau Disease (VHL) or Von Hippel-Lindau Syndrome is a rare genetic disorder caused by a...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2022

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use
open close
CONSULT A DOCTOR
I have read and I do accept terms of use - Telemedicine

Advantage Medindia: FREE subscription for 'Personalised Health & Wellness website with consultation' (Value Rs.300/-)