Rodney DeKoter, an Associate Professor of Microbiology and Immunology at Western’s Schulich School of Medicine & Dentistry and a scientist with the Children’s Health Research Institute, and his team were investigating gene changes responsible for the onset of acute lymphoblastic leukemia (ALL), a blood cancer that is the leading cause of cancer-deaths in children, when the discovery was made.
The study, published this week in the Journal of Immunology, demonstrates that reduced expression of the Bruton Tyrosine Kinase (BTK) gene plays a key role in ALL. DeKoter and Darah Christie, postdoctoral fellow and lead author, showed that a reduction in BTK is associated with the onset of ALL.
Conversely, when DeKoter and his team forced the expression of the gene in culture, it caused the leukemia cells to stop growing and die.
“Our studies showed that a gene-therapy type approach in the cultured cells killed the cancer cells, suggesting that this gene may be important for preventing this form of childhood leukemia,” said DeKoter.
BTK has been extensively studied in human populations because of its well-known association to a primary immunodeficiency called X-linked agammaglobulinemia. “BTK is a famous protein because a mutation in this gene is the most common cause of this type of human immunodeficiency,” DeKoter said. “Our study shows that the gene also plays an important role in leukemia and uncovers an unexpected link between immune deficiency and leukemia.”
The study was funded by the Leukemia & Lymphoma Society of Canada.
PU.1 Opposes IL-7–Dependent Proliferation of Developing B Cells with Involvement of the Direct Target Gene Bruton Tyrosine Kinase, Darah A. Christie,1, Li S. Xu,1, Shereen A. Turkistany, Lauren A. Solomon, Stephen K. H. Li, Edmund Yim, Ian Welch, Gillian I. Bell, David A. Hess and Rodney P. DeKoter, Journal of Immunology, doi:10.4049/jimmunol.1401569, published online 10 December 2014.
Source: Western University