Navigation Links
Mutation in gene IDH a possible target for AML treatment
Date:7/13/2012

Many patients with acute myeloid leukemia (AML) share a mutation in a gene called IDH. A University of Colorado Cancer Center study published this week in the journal Leukemia & Lymphoma shows that this IDH mutation may be the first domino in a chain that leads to a more aggressive form of the disease.

"In fact, it's not IDH itself that causes the problem," says Dan Pollyea, MD, MS, investigator at the CU Cancer Center and assistant professor of hematologic oncology at the University of Colorado School of Medicine. Rather, the mutation in IDH leads to exponentially higher blood levels of a protein called 2-hydroxyglutarate. This protein "mucks up," as Pollyea says, other genes that in turn promote cancer or fail to inhibit its growth.

The recent study shows that AML patients in remission who retain high levels of 2-hydroxyglutarate due universally to IDH mutation are much more likely to relapse than patients without similarly elevated levels.

The chain of causation includes another couple links.

"2-hydroxyglutarate reduces genes' ability to regulate themselves," says Pollyea. Over time genes accumulate gunk in the form of methylation these methyl groups attach to silence parts of gene promoters, helping to decide which genes are and are not turned into proteins. Too much methylation is associated with many cancers, including AML. And 2-hydroxyglutarate turns off one of the body's methylation-regulating genes.

So an IDH mutation leads to high 2-hydroxyglutarate, leads to bad gene regulation, leads to hypermethylation, leads to AML.

Pollyea hopes to stop the first domino from falling by targeting IDH mutations. "Imagine screening for patients prospectively and then if they have the mutation, we could use something like an IDH inhibitor," Pollyea says. Turn off this mutation and doctors may be able to turn of the disease, or at least its most aggressive characteristics.

But the genetic testing for IDH mutation is currently costly and time consuming. And so Pollyea hopes to identify patients with the IDH mutation by looking downstream tests for blood-levels of 2-hydroxyglutarate being developed at the CU Cancer Center could determine the patients most likely to benefit from an IDH inhibitor.

Finally, Pollyea and colleagues including molecular biologist James DeGregori, PhD, are exploring novel ways to target the IDH mutation. "I think that even beyond the very real promise of IDH inhibitor drugs, this is a potential weak spot for AML that can be targeted in a number of ways," Pollyea says.

Pollyea also points out that IDH mutations were first discovered in brain tumors and have also been found in other cancers. A technique targeting IDH mutation in AML may have wide-ranging implications for a variety of cancers.


'/>"/>

Contact: Garth Sundem
garth.sundem@ucdenver.edu
University of Colorado Denver
Source:Eurekalert

Related medicine news :

1. KRAS gene mutation and amplification status affects sensitivity to antifolate therapy
2. Researchers Find Gene Mutations That May Be a Key to Autism
3. Mayo Clinic breast cancer study finds new type of mutation
4. Scientists make breakthrough in bile duct cancer with discovery of new gene mutations
5. Cancer may require simpler genetic mutations than previously thought
6. Mutations impair childhood growth and development by disrupting organization of chromosome pairs
7. Study sheds new light on role of genetic mutations in colon cancer development
8. Mutations in JAK3 gene identified in subtype of lymphoma provide potential drug target
9. Study finds new gene mutations that lead to enlarged brain size, cancer, autism, epilepsy
10. Gene Mutation Linked to Facial, Skull Abnormalities
11. Possible new cancer treatment identified
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... ... June 27, 2016 , ... Quality metrics are proliferating in cancer care, and ... in the eye of the beholder, according to experts who offered insights and commentary ... of Managed Care. For the full issue, click here . , For the ...
(Date:6/26/2016)... ... June 26, 2016 , ... Many women are ... with endometriosis. These women need a treatment plan to not only alleviate symptoms ... can help for preservation of fertility and ultimately achieving a pregnancy. The specialists ...
(Date:6/25/2016)... ... June 25, 2016 , ... First Choice Emergency Room , the largest ... as the Medical Director of its new Mesquite-Samuell Farm facility. , “We are ... Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical Director of First Choice Emergency ...
(Date:6/24/2016)... ... June 24, 2016 , ... A recent article published ... unfamiliar with. The article goes on to state that individuals are now more comfortable ... less common operations such as calf and cheek reduction. The Los Angeles area medical ...
(Date:6/24/2016)... ... June 24, 2016 , ... Global law firm Greenberg Traurig, P.A. announced that ... chosen by their peers for this recognition are considered among the top 2 percent ... special honors as members of this year’s Legal Elite Hall of Fame: Miami ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... 24, 2016  Arkis BioSciences, a leading innovator ... more durable cerebrospinal fluid treatments, today announced it ... funding is led by Innova Memphis, followed by ... private investors.  Arkis, new financing will accelerate the ... market release of its in-licensed Endexo® technology. ...
(Date:6/23/2016)... DUBLIN , June 23, 2016 ... "Dialysis Devices Global Market - Forecast to 2022" report ... is the treatment method for the patients with kidney failure, ... and excess fluid from the patient,s blood and thus the ... sodium, potassium and chloride in balance. Increasing ...
(Date:6/23/2016)... 23, 2016 Research and Markets ... Market by Type (Organic Chemical (Sugar, Petrochemical, Glycerin), Inorganic ... Coating, Parenteral) - Global Forecast to 2021" report ... The global pharmaceutical excipients market is projected to ... of 6.1% in the forecast period 2016 to 2021. ...
Breaking Medicine Technology: