Navigation Links
New leukemia signal could point way to better treatment, Stanford researchers find
Date:9/17/2008

STANFORD, Calif. - Cancer researchers at the Stanford University School of Medicine have discovered a promising new chemotherapy target for a deadly form of leukemia. Their discovery hinges on a novel "double agent" role for a molecular signal that regulates cell growth.

The rogue signal, glycogen synthase kinase 3, was previously found to halt uncontrolled cell growth, preventing several forms of cancer. It also keeps growth of healthy cells in check. But new data show that GSK3 fuels a deadly form of white blood cell cancer, which accounts for five to 10 percent of child and adult leukemias and more than three-quarters of leukemias diagnosed in infants.

"This finding was quite unexpected," said Michael Cleary, MD, senior author of a paper describing the discovery. "GSK3 has never been implicated in promoting cancer." Cleary is a professor of pathology and of pediatrics and a member of the Stanford Cancer Center. The research will appear online in Nature on Sept. 17.

Cleary's team discovered that inhibiting GSK3 combats leukemias caused by mutated MLL genes. MLL, an acronym for "mixed-lineage leukemia," refers to an unusual feature of these deadly cancers. Most leukemias begin in just one of the body's two white blood cell factories, either the lymph nodes or the bone marrow. But in mixed-lineage leukemias, the bad cells can show markers from both kinds of tissue.

Newly diagnosed leukemia patients have their cancer cells tested to see which genes are driving the cancer. Mutated MLL genes are viewed as a bad prognostic marker, Cleary said.

"There is intense interest in coming up with better ways to treat these patients," he said. Cleary's findings indicate GSK3 may be an effective target for future leukemia drugs.

The first hint of GSK3's role came from petri-dish tests on cancer cells. Postdoctoral scholar Zhong Wang, PhD, treated dishes of different kinds of cancer cells with a battery of chemicals that inhibit various cell signals. When a GSK3 inhibitor clobbered cells with mutant MLL genes, Wang realized his work was cut out for him.

"I was excited, but I knew I'd have to do lots of work to confirm the finding," he said. "Most people say GSK3 cannot be a cancer target." That's because of earlier discoveries that showed GSK3 slowed malignancies such as colon cancer.

But Wang's extensive follow-up experiments confirmed GSK3 drove leukemia. For instance, he gave the psychiatric drug lithium, a weak GSK3 inhibitor, to mice with MLL-gene leukemia. Mice that got lithium lived longer than those that did not.

Now that the team knows GSK3 is a potential anti-leukemia target, they're studying how the signal revs up cancer.

They're also starting the hunt for high-potency GSK3 inhibitors that could safely be given to humans. The signal is an especially promising leukemia drug target, the researchers said, because GSK3 normally slows the growth of healthy bone marrow stem cells. Thus, it's possible that giving GSK3 inhibitors will have a double-whammy effect on leukemia, killing the cancerous white blood cells and promoting growth of healthy stem cells, such as those given in a bone marrow transplant.

"Most current cancer drugs target both the normal and the aberrant cells," Cleary said. It would be a big advantage in cancer treatment if a drug were developed that could selectively kill cancer but help healthy cells grow. Of course, the danger with GSK3 inhibitors would be that they might also cause other cancers if given long-term. Cleary said it's too early to tell if or how a new drug might skirt that problem.

"There will be a lot of hard work required to get better anti-GSK3 compounds, test them in preclinical models and translate them to human trials," he said.


'/>"/>

Contact: Erin Digitale
digitale@stanford.edu
650-724-9175
Stanford University Medical Center
Source:Eurekalert

Related medicine news :

1. The Leukemia & Lymphoma Society: Standing Up to Cancer for 60 Years
2. Stater Bros. Raises $200,000 for the Leukemia & Lymphoma Society
3. Methadone Kills Resistant Leukemia Cells
4. FDA Accepts Gentas NDA Amendment as Complete Response for Genasense(R) Treatment of Chronic Lymphocytic Leukemia
5. Leukemia drug could save lives of stroke patients
6. Math could help cure leukemia
7. Gene mutation improves leukemia drugs effect
8. Microenvironment a main driver of aggressive multi-lineage leukemia disease type
9. Clinical study shows biological and clinical activity in relapsed leukemia patients
10. Vion Pharmaceuticals Announces Presentation of Data from Phase III Trial of Cloretazine(R) (VNP40101M) and Cytarabine in Relapsed Acute Myelogenous Leukemia at the ASCO(R) Annual Meeting
11. UCLA researchers identify leukemia stem cells
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... June 27, 2016 , ... ... health professionals, announced today its affiliation with Tennessee Counseling Association. This ... the network of the Tennessee Counseling Association, adding exclusive benefits and promotional offers. ...
(Date:6/26/2016)... (PRWEB) , ... June 27, 2016 , ... Quality metrics ... yet in many ways they remain in the eye of the beholder, according to ... a publication of The American Journal of Managed Care. For the full issue, ...
(Date:6/26/2016)... NC (PRWEB) , ... June 26, 2016 , ... Brent Kasmer, a legally blind and ... to be personalized through a fitness app. The fitness app plans to fix the two ... currently only offer a one size fits all type program , They don’t ...
(Date:6/25/2016)... ... June 25, 2016 , ... The temporary closing of Bruton Memorial Library on June 21 due ... up a new, often overlooked aspect of head lice: the parasite’s ability to live away ... a common occurrence, but a necessary one in the event that lice have simply gotten ...
(Date:6/25/2016)... , ... June 25, 2016 , ... ... and non-athletes recover from injury. Recently, he has implemented orthobiologic procedures as a ... area —Johnson is one of the first doctors to perform the treatment. Orthobiologics ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... Mass. , June 24, 2016   Pulmatrix, ... pharmaceutical company developing innovative inhaled drugs, announced today that ... Russell Investments reconstituted its comprehensive set of ... "This is an important milestone for Pulmatrix," ... will increase shareholder awareness of our progress in developing ...
(Date:6/23/2016)... BEVERLY HILLS, Calif. , June 23, 2016 ... faced the many challenges of the current process. Many of ... option because of the technical difficulties and high laboratory costs ... would have to offer it at such a high cost ... to afford it. Dr. Parsa Zadeh , ...
(Date:6/23/2016)... June 23, 2016 Capricor ... ), a biotechnology company focused on the discovery, ... that patient enrollment in its ongoing randomized HOPE-Duchenne ... exceeded 50% of its 24-patient target. Capricor expects ... third quarter of 2016, and to report top ...
Breaking Medicine Technology: