INDIANAPOLIS—A significant portion of people over the age of 50 have mutations in their blood cells that are associated with leukemia. However, only a small percentage of these otherwise normal people go on to develop leukemia. It is unclear what leads to the development of leukemia in the small portion of people who have pre-leukemic mutations, but Indiana University School of Medicine researchers have found that inflammation can have a big impact on the function of these cells.
In a study published in the journal “Cell Stem Cell”, IU researchers found that inflammation can play a significant role in the growth and survival of stem cells bearing pre-leukemic mutations, such as TET2.
The TET2 mutation in stem cells and progenitor cells results in high levels of expression of a long non-coding RNA called Morrbid. The study demonstrated that Morrbid allows pre-leukemic cells to survive and spread in response to inflammation and can induce the development of clonal hematopoiesis.
“Not only does clonal hematopoiesis due to pre-leukemic mutations increase the risk of blood related cancer, these mutations have also been associated with higher rates of cardiovascular disease, suggesting an association between mutations in blood cells and chronic disease,” said Reuben Kapur, PhD, lead investigator of the study. “So it’s in our best interest to stop its progression.”
The study identified two molecules that can be blocked in order to mitigate clonal hematopoiesis. Using drug compounds provided by Apexian Pharmaceuticals and Novartis Pharmaceuticals, the group partially inhibited clonal hematopoiesis in animal models with the TET2 mutation and high levels of Morrbid.
Using the TET2 mutation as a biomarker, physicians may soon perform genetic sequencing to identify and prevent disease development in high-risk individuals. The study suggests that the compounds provided by Apexian and Novartis may reduce the risk for full blown leukemia and cardiovascular disease in people with clonal hematopoiesis or the pre-leukemic TET2 mutation.
Kapur and Mark Kelley, PhD, have secured a patent on the molecule for the treatment of leukemia. Next, researchers will examine how other risk factors—such as diabetes and obesity—interact with the TET2 mutation in the development of cardiovascular disease and leukemia.