Navigation Links
'Vicious circle' offers new acute leukemia treatment target
Date:4/13/2010

COLUMBUS, Ohio Researchers have identified a self-feeding "vicious circle" of molecules that keeps acute leukemia cells alive and growing and that drives the disease forward.

The findings suggest a new strategy for treating acute myeloid leukemia (AML), one that targets this molecular network and lowers the amount of a protein called KIT, say researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James) who conducted the study.

Published in the April 13 issue of the journal Cancer Cell, the study described a new network of protein and microRNA molecules that, when imbalanced, contributes to abnormal KIT protein abundance and favors leukemia development. The researchers were also able to target this network with therapeutic drugs.

"We now understand the mechanism responsible for making so much KIT protein in AML cells, and we believe that targeting that mechanism and reducing the amount of that protein will prove to be a more effective therapy for this disease than the current standard of care," says study leader Dr. Guido Marcucci, professor of internal medicine and an AML specialist at the OSUCCC-James.

AML strikes 12,800 Americans, killing 9,000 of them each year. More than 80 percent of those cases have elevated levels of KIT protein.

Currently, doctors treat AML using standard chemotherapy. Drugs that target and block the activity of the KIT protein are being tested in clinical trials. These agents, called tyrosine kinase inhibitors, bind to the protein and stop disease progression, but they can lose their effectiveness when new mutations that arise during the course of the disease alter the protein.

"Our study suggests that the amount of KIT protein in cancer cells is as important as its activity, and we discovered that the amount of the protein is controlled by a circular network of molecules that has many points of entry," says senior co-leader Dr. Ramiro Garzon, assistant professor of internal medicine and an AML specialist at the OSUCCC-James.

"These findings provide a strong rationale for the use and development of drugs that target the components of this network rather than focusing on the activity of KIT alone."

Marcucci, Garzon, first author Shujun Liu, assistant professor of internal medicine, and their colleagues began this study by showing that patients with mutations in the KIT gene in their leukemic cells had the highest levels of the KIT protein in those cells, and that these patients also had the poorest survival.

"This told us that the amount of the protein in cancer cells is important to the disease process," Liu says.

Using laboratory-grown AML cells, the researchers identified the series of molecules that control the amount of KIT protein, showing for the first time that a microRNA called miR-29b, along with several well-known cancer-related genes, regulate KIT production.

Normally, these elements work in a balanced fashion to produce the correct amount of KIT protein for healthy cell survival and proliferation. That normal balance is derailed when gene mutations or other genetic damage occurs in the network and promotes the overproduction of the KIT protein.

"It becomes a vicious circle because no matter where genetic damage occurs, the result is the same overactivation of the circle, overexpression of the KIT protein, and proliferation of leukemic cells," Liu says.

Using a mouse model, the researchers showed that raising the amount of mutated KIT protein causes leukemia, and drugs that target the network lower the amount of that protein and drive the leukemia into remission. These drugs included proteasome inhibitors, histone deacetylase inhibitors, along with inhibitors of molecules called NFĸB and Sp1.


'/>"/>

Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

Related biology news :

1. Tall tale of giant stingray circles the globe
2. Nations largest organization of ecologists offers expert database
3. Fertility industry offers big money to recruit desirable egg donors at top universities
4. DNA nanotechnology breakthrough offers promising applications in medicine
5. New microscopy technique offers close-up, real-time view of cellular phenomena
6. Society of Interventional Radiology Press offers new edition of patient care resource
7. The sea squirt offers hope for Alzheimers sufferers
8. TriCipher myOneLogin SignatureBook Offers Digital Signatures On-Demand
9. Brain study offers insight into causes of autism
10. Synthetic biology offers new opportunities for interdisciplinary collaboration
11. Society of Interventional Radiology hosts oncology therapies Webinar, offers resources
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/22/2016)... 2016 http://www.researchandmarkets.com/research/p74whf/global_biometrics ... "Global Biometrics Market in Retail Sector ... --> http://www.researchandmarkets.com/research/p74whf/global_biometrics ) has announced ... Market in Retail Sector 2016-2020" report ... Research and Markets ( http://www.researchandmarkets.com/research/p74whf/global_biometrics ) has ...
(Date:1/20/2016)... 20, 2016   MedNet Solutions , an innovative ... of clinical research, is pleased to announce the attainment ... are the result of the company,s laser focus on ... , it,s comprehensive, easy-to-use and highly affordable cloud-based ... Key MedNet growth achievements in 2015 include: ...
(Date:1/15/2016)... Puerto Rico , Jan. 15, 2016 ... big and small to find new ways to ensure ... culture. iOS and Android ... based on biometrics, transforming it into a hardware authorization ... that users swipe their fingerprint on their KodeKey enabled ...
Breaking Biology News(10 mins):
(Date:2/4/2016)... , Feb. 4, 2016 ContraVir Pharmaceuticals, Inc. ... the development and commercialization of targeted antiviral therapies, announced ... Investor Conference 2016, to be held February 8-9, 2016, ... Group,s 2016 Disruptive Growth & Healthcare Conference, taking place ... 10-11, 2016. James Sapirstein , Chief Executive ...
(Date:2/4/2016)... ... February 04, 2016 , ... ... supplier of Semantic Graph Database technology has been recognized As “ Best in ... Corporate America Magazine. , “At Corporate America, it’s our priority to showcase prominent ...
(Date:2/3/2016)... DIEGO , Feb. 3, 2016   ... company with the first pluripotent stem cell-derived islet ... diabetes in clinical-stage development, today announced that ViaCyte ... Pharmaceutical Companies of Johnson & Johnson, have agreed ... group into ViaCyte.  The agreement provides ViaCyte with ...
(Date:2/3/2016)... Ascendis Pharma A/S (Nasdaq: ASND ), ... TransCon technology to address significant unmet medical needs, today ... Leerink Partners Global Healthcare Conference Location: , Waldorf ... 2016 Time:  , 11:55am EST www.ascendispharma.com ... An audio webcast of this event will be posted ...
Breaking Biology Technology: