PHILADELPHIA There are many kinds of cancers of the immune system, but one, Activated B-Cell Diffuse Large B-Cell Lymphoma, or ABC-DLBCL, is particularly common and pernicious. Researchers at the University of Pennsylvania's School of Veterinary Medicine have shown for the first time that dogs that develop this disease spontaneously share the same aberrant activation of a critical intracellular pathway with humans. They also found that a drug designed to disrupt this pathway helps to kill tumor cells in the dogs' cancerous lymph nodes.
The research was conducted by Nicola Mason, assistant professor of medicine at Penn Veterinary, along with Michael J. May, associate professor of pharmacology; postdoctoral fellow Anita Gaurnier-Hausser; and veterinary clinical pathologist Reema Patel.
Their work was published in the journal Clinical Cancer Research.
B-cells are the part of the immune system that produce antibodies and protect the body against invading microorganisms or allergens. In ABC-DLBCL, the intracellular signaling pathway involved in B-cell activation and proliferation is, as the name of the disease suggests, constantly activated.
"This signaling pathway, called NF-kappaB, is critical in immune function; following an encounter with antigen, lymphocytes need to be activated and proliferate so that there are sufficient numbers to deal with the invading organism," Mason said. "But in humans with ABC-DLBCL, and also in dogs with spontaneous DLBCL, this pathway is constitutively active and drives lymphocytes to proliferate continuously."
Moreover, these malignant B-cells are resistant to apoptosis, or cell death. Their unchecked growth is the basis of the lymph node tumors that are a hallmark of the disease.
For many years, researchers have been investigating ways of interrupting the malfunctioning pathway that forms the tumors and provides resistance to chemotherapy-induced cell death. In order to
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University of Pennsylvania