The study, led by investigators at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), shows that large granular lymphocyte leukemia can occur in a small subset of white blood cells called NKT cells. NKT cells share features of immune cells called T lymphocytes and features of immune cells called natural killer (NK) cells.
The discovery, published online in the Journal of Clinical Investigation, arose from studies investigating why a mouse strain engineered to overexpress interleukin-15 often develops large granular lymphocyte leukemia, a disease more common in Asia than the United States, and it points to new ways to prevent the malignancy.
The researchers show that, in mice and in humans, the novel subset of NKT cells responsible for large granular lymphocyte leukemia are marked on their surface by a protein called NKp46. Only small numbers of these cells are present in mice and in humans. The study further shows that overexpression of interleukin-15 can drive these cells but not others to become leukemic.
“These novel NKT cells represent a small white-blood-cell population in normal mice or healthy humans, but they have the potential to develop into large granular lymphocyte leukemia under certain circumstances, such as a high interleukin-15 environment,” says first author Jianhua Yu, a research scientist with the OSUCCC – James.
“Our work suggests that targeting interleukin-15 signaling and NKp46 might offer a new way to prevent this leukemia as we learn more about who is susceptible,” notes principal investigator Dr. Michael A. Caligiuri, director of Ohio State’s Comprehensive Cancer Center and CEO of the James Cancer Hospital and Solove Research Institute. “In fact, we show that using an antibody to block interleukin-15 prevents large granular lymphocyte leukemia development in this mouse model.”
Funding from the National Cancer Institute supported this research.
Other researchers involved in this study were Takeki Mitsui, Min Wei, Hsiaoyin Mao, Jon Butchar, Jianying Zhang, Anjali Mishra, Christopher Alvarez-Breckenridge, Xingluo Liu, Shujun Liu, Rossana Trotta, Guido Marcucci, Don M. Benson Jr., and Susheela Tridandapani of Ohio State; Akihiko Yokohama, of Gunma University, Maebashi, Japan; and Mithun Vinod Shah and Thomas P. Loughran Jr., of Penn State Hershey Cancer Institute.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute cancer.osu.edu is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top cancer hospitals in the nation, The James is the 205-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only seven funded programs in the country approved by the NCI to conduct both Phase I and Phase II clinical trials.
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