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Biochemical cascade causes bone marrow inflammation, leading to serious blood disorders
Date:7/3/2014

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.


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Contact: Eric Schoch
eschoch@iu.edu
316-274-8205
Indiana University
Source:Eurekalert  

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