Study shows cause of and potential cure for aggressive leukemia

In a recent study, excessive levels of interleukin-15 (IL-15) initiated large granular lymphocyte (LGL) leukemia, a rare and usually fatal form of cancer, but also represented a promising therapeutic target.

The body normally releases IL-15, a hormone-like substance, to stimulate the development, survival, and proliferation of natural-killer cells. These immune cells destroy cancer cells as well as virus-infected cells. The new research from Michael A. Caligiuri and colleagues demonstrates that when IL-15 is present in high amounts for prolonged periods, such as during chronic inflammation, it can cause LGLs to become cancerous.

“We know that inflammation can cause cancer, but we don't know the exact mechanism,” commented Caligiuri in a statement issued by Ohio State University Medical Center in Columbus, Ohio, to announce the study findings, which were published in the journal Cancer Cell (2012;22[5]:645-655). Caligiuri is the CEO of The James Cancer Hospital and Solove Research Institute at Ohio State as well as director of Ohio State's Comprehensive Cancer Center.

In their study, the researchers used a mouse model of LGL leukemia as well as cells isolated from patients with the disease to demonstrate one way in which inflammation can cause cancer. They found that in this case, the malignant transformation begins when IL-15 attaches to receptors on the surface of normal LGLs. This action boosts levels of Myc, a cancer-causing protein inside the cells. In addition to contributing to chromosome instability and additional gene mutations, the high Myc levels also activate DNA methylation, which turns off genes that normally suppress cancer growth.

One investigator on the team developed a liposomal formulation of the proteosome inhibitor bortezomib, which shut down the cancer-causing pathway, potentially curing the malignancy: All leukemic mice that received the liposomal bortezomib were still alive 130 days later, whereas all control mice had died within 60 to 80 days.

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