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.
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.
(Photo Credit: Indiana University)
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.
(Photo Credit: Indiana University)
Source: Indiana University