Navigation Links
Targeting errant immune system enzyme kills myelodysplastic cells
Date:7/8/2013

CINCINNATI -- Scientists have successfully targeted a malfunctioning immune system enzyme to kill diseased cells from patients with myelodysplastic syndrome (MDS) -- a blood disorder and precursor to leukemia.

Reporting their results July 8 in Cancer Cell, researchers say their successful laboratory tests in human MDS cells and mouse models of MDS provide a molecular target for designing new drugs to battle a syndrome with few effective treatments.

"There is an urgent need to develop new targeted therapies that can eliminate MDS-initiating clone cells and provide a durable therapeutic response," said Daniel Starczynowski, PhD, lead researcher and a member of the Division of Experimental Hematology and Cancer Biology at Cincinnati Children's Hospital Medical Center. "Not only does our research implicate errant immune system signaling in MDS cells, it strongly indicates that inhibiting the function of this hijacked immune pathway may become an effective treatment option for MDS."

MDS is a group of syndromes in which a person's immature blood cells (blood stem cells) do not mature into healthy red or white blood cells. Instead, the immature cells die off in the bone marrow or blood, leaving an insufficient number of healthy cells in the body. This can cause infections, anemia, bleeding disorders or acute myeloid leukemia (AML).

MDS can affect children but is more common in people over the age of 60. Some research studies indicate the prevalence of MDS is increasing as life expectancies become longer. Caused by various gene mutations, the only cure for MDS is bone marrow transplant a risky procedure that is often not a viable option, especially for older people.

Starczynowski and his colleagues wanted to identify a molecular target that affects MDS-related biological pathways. Their goal was to inhibit the molecule to see if that would suppress the duplication and expansion of MDS cells.

They worked from past studies that analyzed elevated gene expression in MDS cases and then conducted their own analyses of MDS and AML patient cells. The research team verified that an immune system enzyme called IRAK1 (Interleukin Receptor Associated Kinase-1) is highly over-expressed and hyper-activated in about 25 percent of MDS/AML cells.

The researchers then tested the effect of blocking IRAK1 on human MDS cells, on mouse models of human MDS and on normal human CD34+ blood cells. They used both direct genetic inhibition and a small-molecule inhibitor of IRAK1 (called IRAK-Inh) that was developed initially as prospective treatment for autoimmune disease and chronic inflammation.

Both genetic and pharmacologic inhibition of IRAK1 was effective at slowing the progression of human MDS cells and in mouse models of the disease. Inhibiting IRAK1 also had no effect on normal human CD34+ blood cells, showing it selectively targets MDS cells.

A possible shortcoming to IRAK-Inh treatment was discovered when researchers noticed it was not effective at overcoming a pro-cancer survival gene called BCL2. In some cell lines treated with IRAK-Inh, BCL2 genes became overexpressed in an effort to compensate for and work around the experimental treatment a common occurrence in certain cancer therapies.

Researchers responded by testing a collaborative treatment strategy, combining IRAK-Inh with an inhibitor of BCL2 called ABT-263. The combination treatment was effective at selectively targeting and killing MDS cells without harming normal blood cells.

Starczynowski cautioned that laboratory tests in mouse models and cell cultures do not necessarily translate into treatment for humans. Because IRAK1 is currently thought to be overexpressed in a subset of MDS patients, any prospective drugs targeting the enzyme would in theory benefit only that group.


'/>"/>

Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

Related medicine news :

1. hCGTreatments / Diet Doc hCG Diets & Weight Loss Plans Offer Improved hCG Diet Plans Capable of Targeting Stubborn Belly Fat Now Linked With Decreased Bone Density
2. hCGTreatments / Diet Doc hCG Diets & Weight Loss Plans Now Offer New Weight Loss Diets that Educate Patients, Targeting Weight Gained During Childhood and Adolescence
3. Overcoming resistance to anti-cancer drugs by targeting cell powerhouses
4. Study Shows Dual Targeting of HER2 and HR-positive Metastatic Breast Cancer Improves Survival Rates
5. Drugs targeting blood vessels may be candidates for treating Alzheimers
6. Changing shape makes chemotherapy drugs better at targeting cancer cells
7. Cleveland Clinic study shows bariatric surgery restores pancreatic function by targeting belly fat
8. Daimer Ships Steam Pressure Washer For Pest Control Industry Targeting Food Service Kitchens
9. Treatment targeting PI3K may delay resistance to anti-HER2 therapy in breast cancer patients
10. Targeting use of acid-suppressants in hospital patients
11. Spread of cancer cells may be slowed by targeting of protein
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/24/2017)... ... March 24, 2017 , ... Judy Buchanan, co-owner ... in Frederick, MD. Judy says, “I am passionate about sharing Reiki as a ... very difficult and challenging time.” , A Certified Medical Reiki™ Master trained by ...
(Date:3/24/2017)... ... ... “Vintage and Harvest A Cultivation of Christian Love” is the creation of published author, ... his wife, Anna Marie. He and his wife are the proud parents of four ... of “Shadow and Substance.” , “Love, the agape kind, is seen as more than ...
(Date:3/23/2017)... & Seattle, WA (PRWEB) , ... March 23, 2017 , ... ... health emergency and now estimates that there could be four million Zika-related cases in ... epidemics to date with numbers of US cases reported per year skyrocketing to an ...
(Date:3/23/2017)... Alexandria, Virginia (PRWEB) , ... March 23, 2017 ... ... quality public health services to their communities, 16 more public health departments have ... This week’s decisions bring another 4.5 million people into the expanding network of ...
(Date:3/23/2017)... ... 2017 , ... The IoT (Internet of Things) is revolutionizing the way the ... on businesses and individual consumers alike. Laboratories can maximize their profit margin by ... from $4 trillion to $11 trillion dollars by the year 2025. McKinsey expects the ...
Breaking Medicine News(10 mins):
(Date:3/24/2017)... , March 24, 2017 Abdominal Aortic Aneurysm Repair Devices ... by 2022, Globally, registering a CAGR of 5.1% from 2016 to 2022. The endovascular ... to dominate the market during the study period. Continue ... ... ...
(Date:3/24/2017)... Mar. 24, 2017 Research and Markets ... the U.S.: Consumer Strategies" report to their offering. ... Pain ... approach and treat their physical pain, emphasizing consumer survey analysis, ... pain sufferers and adults who have selected illnesses/conditions strongly associated ...
(Date:3/24/2017)... FinancialBuzz.com News Commentary   ... Medical cannabis products around the world are projected to gain popularity. A ... market will reach a value of USD 55.8 billion by 2025. ... growing industry. By the end of 2016, 28 states have now laws ... conservative states like Arkansas and North ...
Breaking Medicine Technology: