Navigation Links
Biochemical cascade causes bone marrow inflammation, leading to serious blood disorders

INDIANAPOLIS -- Like a line of falling dominos, a cascade of molecular events in the bone marrow produces high levels of inflammation that disrupt normal blood formation and lead to potentially deadly disorders including leukemia, an Indiana University-led research team has reported.

The discovery, published by the journal Cell Stem Cell, points the way to potential new strategies to treat the blood disorders and further illuminates the relationship between inflammation and cancer, said lead investigator Nadia Carlesso, M.D., Ph.D., associate professor of pediatrics at the Indiana University School of Medicine.

Bone marrow includes the cells that produce the body's red and white blood system cells in a process called hematopoiesis. The marrow also provides a support system and "home" for the blood-producing cells called the hematopoietic microenvironment. The new research demonstrates the importance of the hematopoietic microenvironment in the development of a group of potentially deadly diseases called myeloproliferative disorders.

"It has been known for years that there are links between inflammation and cancer, but these studies have been challenged by the lack of genetic models, especially for blood-based malignancies," said Dr. Carlesso, a member of the hematologic malignancy and stem cell biology program within the Wells Center of Pediatric Research at IU.

The researchers focused on what happens when there are abnormally low levels of a molecule called Notch, which plays an important role in the process of blood cell production. Using a genetically modified mouse, they found that the loss of Notch function in the microenvironment causes a chain of molecular events that result in excess production of inflammatory factors.

The high levels of inflammation in the bone marrow were associated with the development of a myeloproliferative disorder in the mice. Myeloproliferative diseases in humans can result in several illnesses caused by overproduction of myeloid cells, which are normally are used to fight infections. These diseases can put patients at risk for heart attack or stroke, and frequently progress into acute leukemia and bone marrow failure, which have fatal outcomes. Unfortunately, there are no effective therapies for the majority of myeloproliferative diseases.

When Dr. Carlesso's team blocked the activity of one of the molecules in this biochemical cascade, the myeloproliferative disorder in the mice was reversed. In addition, elevated levels of the blocked molecule were found in samples from human patients with myeloproliferative disease. These findings suggest that developing drugs that target this inflammatory reaction at different key points could be a promising strategy to limit the development of myeloproliferative disease in humans.

The molecular cascade leading to inflammation was not occurring directly in the bone marrow cells that produce blood cells, but in cells of the bone marrow microenvironment, especially in endothelial cells that line the capillaries -- tiny blood vessels -- inside the bone marrow. This was a key discovery, Dr. Carlesso said.

"This work indicates that we need to target not only the tumor cells, but also the inflammatory microenvironment that surrounds them and may contribute to their generation," she said.

"We believe that this combined strategy will be more effective in preventing myeloproliferative disease progression and transformation in acute leukemias."

Dr. Carlesso also noted that the Notch molecule is mostly known as an oncogene -- one that can cause cancer -- and so is often targeted by therapies for other types of cancer. The new research indicates that clinicians need to be aware of the effects that reducing levels of Notch function could have on the blood development process, she said.


Contact: Eric Schoch
Indiana University

Related medicine news :

1. Biological and Biochemical Product Manufacturing in China Industry Research Report – Now Available from IBISWorld
2. New study pinpoints biochemical mechanism underlying fibrosis following glaucoma surgery
3. Cascade Gasket Utilizes the NOVAtime 4000 SaaS Workforce Management System to Manage Business Processes in Real-Time
4. Campus Teamwear Donates Cheer Gear for Cascade AIDS Project Fundraiser
5. Hot Pot with chicken causes campylobacter infections in Switzerland
6. Causes of serious pain syndrome closer to discovery
7. Research proves shock wave from explosives causes significant eye damage
8. Healthy component of red wine, resveratrol, causes pancreatic abnormalities in fetuses
9. Water pipe smoking causes significant exposure to nicotine and cancer-causing agents
10. TB lung infection causes changes in the diversity of gut bacteria in mice
11. Long-term antibiotic treatment for Q fever causes weight gain
Post Your Comments:
Related Image:
Biochemical cascade causes bone marrow inflammation, leading to serious blood disorders
(Date:6/27/2016)... (PRWEB) , ... June 27, 2016 , ... "FCPX editors ... customizable inside of Final Cut Pro X," said Christina Austin - CEO of Pixel ... style. Final Cut Pro X users can now reveal the media of ...
(Date:6/27/2016)... ... June 27, 2016 , ... ... patient payment industry today announced its strategic partnership with Connance, a healthcare ... , The two companies’ proven, proprietary technology combine to provide health systems, ...
(Date:6/27/2016)... ... June 27, 2016 , ... recently awarded their highest ... . , Millions of individuals in the United States and Canada wear eyeglasses. Once ... to both correct vision and make a fashion statement. Even celebrities use glasses as ...
(Date:6/26/2016)... ... June 26, 2016 , ... On June 10-11, 2016, A Forever Recovery, a ... and World’s Longest Breakfast Table in Battle Creek, MI, where the rehabilitation facility is ... to some of the world’s leading providers of cereal and other breakfast foods. Its ...
(Date:6/26/2016)... ... June 26, 2016 , ... PawPaws brand pet ... product that was developed to enhance the health of felines. The formula is all-natural ... two main herbs in the PawPaws Cat Kidney Support Supplement Soft Chews ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... 23, 2016 Roche (SIX: RO, ROG; OTCQX: ... its Elecsys BRAHMS PCT (procalcitonin) assay as a dedicated ... shock. With this clearance, Roche is the first IVD ... solution for sepsis risk assessment and management. ... and PCT levels in blood can aid clinicians in ...
(Date:6/23/2016)... DUBLIN , June 23, 2016 ... "Key Pharma News Issue 52" report to their offering. ... need in influenza treatment creates a favourable commercial environment for ... and growing patient base that will serve to drive considerable ... flu vaccine would serve to cap sales considerably, but development ...
(Date:6/23/2016)... Ill. and INDIANAPOLIS , ... students receiving a Lilly Diabetes Tomorrow,s Leaders Scholarship is ... 2016 scholarship winners, announced today online at ... let type 1 diabetes stand in the way of ... has supported the Foundation,s scholarship program since 2012, and ...
Breaking Medicine Technology: