Inimical Inflammation

Study Shows How Chronic Inflammation Can Cause Cancer

Anjali MishraWhen present at high levels, a hormone-like substance produced by the body to promote inflammation can cause an aggressive form of leukemia, OSUCCC – James researchers have found.

Their study shows that high levels of interleukin-15 (IL-15) alone can cause large granular lymphocytic (LGL) leukemia, a rare and usually fatal disease, in an animal model. The researchers also developed a treatment for the leukemia that showed no discernible side effects in the animal model.

In addition, their findings show that IL-15 is overexpressed in patients with LGL leukemia and that it causes similar cellular changes, suggesting that the treatment should also benefit people with the malignancy.

“We know that inflammation can cause cancer, but we don’t know the exact mechanism,” says co-senior author Michael A. Caligiuri, MD, director of the OSUCCC and CEO of The James. “Here, we show one way it can happen, and we used that information to potentially cure the cancer.”

The research was developed and carried out in collaboration with co-senior author Guido Marcucci, MD, associate director for translational research at the OSUCCC – James. “In this study, we show the joined role of genetic instability and microRNAs in leading directly to cancer,” says Marcucci, who notes that this work is part of a long history of research at the OSUCCC – James that is revealing the role of microRNA in cancer and its potential as a therapeutic target.

 “Once we understood how this inflammatory hormone causes this leukemia, we used that information to develop a treatment by interfering with the process,” says first author Anjali Mishra, PhD, a postdoctoral researcher in Caligiuri’s laboratory.

Caligiuri, Marcucci and Mishra were joined in this study by Robert Lee, PhD, professor of Pharmaceutics and Pharmaceutical Chemistry in Ohio State’s College of Pharmacy, and a group of collaborators.

Published in the journal Cancer Cell.

NIH/National Cancer Institute grants CA16058, CA95426, CA68458, CA09338, CA140158, CA102031 and CA149623, and National Science Foundation grant EEC-0914790 supported this research.

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