Mutation in gene IDH a possible target for AML treatment

July 13, 2012 in Cancer

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 . "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 could determine the 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.

Provided by University of Colorado Denver search and more info website

5 /5 (1 vote)  

Rank 5 /5 (1 vote)
Relevant PhysicsForums posts

More news stories

New fluorescent tools for cancer diagnosis

In recent years, microRNAs (miRNAs) and other non-coding RNAs are small molecules that help control the expression of specific proteins. In recent years they have emerged as disease biomarkers. miRNA profiles have been used ...

Cancer created 17 hours ago | popularity not rated yet | comments 0

Modulating the immune system to combat metastatic cancer

Cancer cells spread and grow by avoiding detection and destruction by the immune system. Stimulation of the immune system can help to eliminate cancer cells; however, there are many factors that cause the immune system to ...

Cancer created 17 hours ago | popularity 5 / 5 (1) | comments 0

Scientists put bowel cancer under the microscope

Researchers from London's Kingston University have begun a two-year study which could help prolong the lives of people with colorectal tumours.

Cancer created 20 hours ago | popularity 5 / 5 (1) | comments 0

Researcher identifies breast cancer fighting hormone

Transformative research from Western University has identified new hormones in the body which may suppress breast cancer and stimulate the regression of breast tumors.

Cancer created 21 hours ago | popularity 5 / 5 (2) | comments 0

Ground breaking cancer research finds immune system link

(Medical Xpress)—Curtin University researchers have found evidence that targeting specific cells in the body can reverse the effects of cancer on the immune system.

Cancer created 21 hours ago | popularity 5 / 5 (4) | comments 0


Engineered cytomegalovirus protects monkeys from HIV equivalent

(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...

Researchers identify first drug targets in childhood genetic tumor disorder

Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...

Hormone levels may provide key to understanding psychological disorders in women

Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.

Are there atheists in foxholes? Study says they're the minority

Ernie Pyle – an iconic war correspondent in World War II – reportedly said "There are no atheists in foxholes." A new joint study between two brothers at Cornell and Virginia Wesleyan found that only ...

Going live: Immune cell activation in multiple sclerosis

Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...

Help at hand for people with schizophrenia

How can healthy people who hear voices help schizophrenics? Finding the answer for this is at the centre of research conducted at the University of Bergen.