Navigation Links
Targeting cell pathway may prevent relapse of leukemia
Date:3/25/2010

Boston, Mass. About 40 percent of children and up to 70 percent of adults in remission from acute myelogenous leukemia (AML) will have a relapse. In recent years, doctors have come to believe that this is due to leukemia stem cells, endlessly replicating cancer cells that generate the immature blood cells characteristic of leukemia and are resistant to typical cancer treatments. Now, researchers at Children's Hospital Boston have found a possible way to kill off these cells, and prevent them from initiating a relapse.

The study, published online March 26th in the journal Science, shows that leukemia stem cells cannot thrive without a particular cell pathway, known as the Wnt/beta-catenin pathway, suggesting that targeting this pathway may prevent the growth and development of AML.

"The biggest potential for this study is in suppression of leukemia recurrence by a drug that inhibits beta-catenin," says Scott Armstrong, MD, PhD, of Children's Division of Pediatric Hematology/Oncology and senior author of the study.

Yingzi Wang, PhD, of Children's Division of Pediatric Hematology/Oncology, a member of Armstrong's team and lead author of the study, zeroed in on beta-catenin as an important player in leukemia stem cells by working with two different types of early blood cells blood stem cells, which generate all the different types of blood cells, and granulocyte/macrophage-restricted progenitors, more mature, differentiated cells that only generate certain white blood cells. They did this by activating two genes previously found to induce AML, Hoxa9 and Meis1, then injecting the cells into mice.

Activation of the two genes induced AML in mice injected with the blood stem cells, but not in mice injected with the progenitors. Genetic analyses revealed the progenitors lacked an active beta-catenin pathway. Though this pathway is still active in blood stem cells after a person is born, it plays a vital role only during fetal development, and is completely inactive in more differentiated progenitor cells. This led the team to think beta-catenin was needed for leukemia stem cells to develop, thrive and induce leukemia.

To test this idea, the researchers introduced an active form of beta-catenin into the progenitor cells after activating Hoxa9 and Meis1. Once injected into mice, these progenitor cells later induced leukemia.

The researchers further confirmed the role of beta-catenin by treating mice they had injected with leukemia stem cells with the drug indomethacin, which blocks the beta-catenin pathway. Tests showed the number of leukemia stem cells dwindled in the mice that received the drug. Indomethacin also reduced the number of stem cells in mice with fully-developed leukemia.

Most young children with AML develop the disease as a result of what researchers call mixed lineage leukemia fusion proteins, which can activate the Hoxa9 and Meis1 genes. To see if one of these proteins also affected the beta-catenin pathway, the team treated progenitor cells with the mixed lineage leukemia fusion protein MLL-AF9. MLL-AF9 activated Hoxa9 and Meis1, as well as the beta-catenin pathway, and the mice injected with these progenitor cells developed leukemia. But when the mice were treated with an agent to deactivate the beta-catenin pathway in vivo, the leukemia stem cells could not thrive.

This research suggests that leukemia stem cells need the beta-catenin pathway to survive, and treatments that block this pathway may eradicate the leukemia stem cells and prevent AML patients from having a relapse.

Before these findings can be applied in the clinic, better beta-catenin inhibitors are needed, since it's not known if indomethacin can be given to people with leukemia in high enough doses to wipe out leukemia stem cells without having toxic effects, Armstrong says. The next step for researchers is to determine the reason why leukemia stem cells need the beta-catenin pathway to survive.

"Any step along the pathway is a potential therapeutic opportunity," Armstrong says.


'/>"/>

Contact: Rob Graham
rob.graham@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

Related medicine news :

1. Hacker Attacks Targeting Healthcare Organizations Doubled in the 4th Quarter of 2009 According to SecureWorks Data
2. Targeting brain cancer cell metabolism may provide new treatment
3. With White House Jobs Summit This Week KSBH Unveils New TV Ads Targeting Senators on Health Care
4. First live targeting of tumors with RNA-based technology
5. Targeting cancerous vessels
6. Dana-Farber and Sanford-Burnham Institute license flu-targeting antibodies to Genentech and Roche
7. Targeting leukemia cells gene addiction presents new strategy for treatment
8. Americans for Responsible Health Care Launch Radio Ads Targeting Seven Democrats, Warning The People Are Watching...
9. Targeting blood vessels, immune system may offer way to stop infection-caused inflammation
10. Diversinet Extends Reach of Mobile Healthcare Information With New Product Release Targeting Healthcare Organizations
11. Ganeden Biotech and Pathway International Announce Exclusive Distribution Partnership
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... Little Rock, AR (PRWEB) , ... October 13, ... ... owned firm with locations throughout Arkansas that offers insurance and financial preparation services, ... to benefit the Rock City Rescue organization. , Rock City Rescue is a ...
(Date:10/13/2017)... ... 2017 , ... PurhealthRX , a leading Health and Nutrition Company, is ... to full spectrum CBD oil will revolutionize the rapidly growing CBD market by reducing ... easily incorporated into liquid products, while reducing costs to end users. , The team ...
(Date:10/13/2017)... , ... October 13, 2017 , ... The Visiting Nurse ... Market. Featuring a collection of specialty vendors and unique items from across the nation, ... quality-focused health and wellness services offered by the VNA. The boutique will be ...
(Date:10/13/2017)... ... October 13, 2017 , ... ... Agile Software Development, has been awarded a contract by the Center for Medicare ... (BPA) aims to accelerate the enterprise use of Agile methodologies in a consistent ...
(Date:10/12/2017)... ... , ... Planet Fitness, one of the largest and fastest growing franchisors and ... flagship location in Covington, LA at 401 N. U.S. Highway 190, in January of ... Depot in the Holiday Square shopping center. Its location allows it to serve both ...
Breaking Medicine News(10 mins):
(Date:10/2/2017)... -- Halo Labs announces the European launch of their new low ... MIBio 2017 in Cambridge, U.K on October ... biopharmaceutical samples with unprecedented speed and sensitivity while using far less ... Imaging. ... analysis system ...
(Date:9/27/2017)... -- Commended for their devotion to personalized service, SMP Pharmacy Solutions ... in the South Florida Business Journal,s 50 Fastest-Growing Companies, and ... the national specialty pharmacy has found its niche.  To that ... be honored by SFBJ as the 2017 Power Leader in ... receive his award in October, Bardisa said of the three ...
(Date:9/23/2017)... Sept. 22, 2017 Janssen Biotech, Inc. (Janssen) ... letter from the U.S. Food and Drug Administration (FDA) ... sirukumab for the treatment of moderately to severely active ... clinical data are needed to further evaluate the safety ... active RA. ...
Breaking Medicine Technology: