Oct
3
2007

Serendipity is the word Andrei Thomas-Tikhonenko, PhD, uses to describe a scientific discovery that brings researchers a step closer to finding a cure for B-cell lymphoma, the most common lymphoma that affects dogs and people.

The key, he believes, is shutting off the PAX5 protein, a natural component of B cells, which fight infection. In cancer patients, PAX5 has run amok, he said. In normal bodies, the B cell fights infection and then stops reproducing. In cancer patients, the B cell is activated and then continues to reproduce, thereby causing B cell lymphoma, explained Thomas-Tikhonenko. His research was published in the September 2007 issue of The Journal of Clinical Investigation.

Thomas-Tikhonenko, who has studied the PAX5 gene and protein since 2003 and tested his theory on mice and human tumors, recently started working with two veterinarians - Karin Sorenmo, DVM, DACVIM, ECVIM; and Erika Krick, VMD, ACVIM – at the University of Pennsylvania.

“We are very interested in that [dog] model. It is a very good model for the disease… better than the mouse,” Thomas-Tikhonenko explained.

The discovery was made possible through his collaboration with Diana Cozma, MD, and two pathologists from Oxford, who had a bank of B cell tumors. “For some serendipitous reason, the PAX5 had been turned off in some of those cells and the tumors were forming poorly,” Thomas-Tikhonenko said. “When the protein was added back, rapid tumor growth resumed” he added.

Using an automobile analogy, Thomas-Tikhonenko explained that if you are trying to discern whether gas makes a car run, you must wait until a car has run out of gas and cannot run, and then refuel it to prove that gas fuels cars. By the same token, to prove that PAX5 causes lymphomas to develop faster, you need a lymphoma that doesn’t produce PAX5. Such a lymphoma was identified by Duonan Yu, MD, PhD, a scientist at Children’s Hospital of Philadelphia.

“We know that if you can shut off X5, you can seriously slow down tumor growth,” said Thomas-Tikhonenko. “We don’t know how. We are working on this.”

Veterinarians at the Mari Lowe Center for Comparative Oncology are helping in this research. Published data from the 1990s shows that canine lymphoma accounts for five percent of reported malignant canine neoplasms and has an incident rate of 25 in 100,000 dogs per year, said Thomas-Tikhoneno.

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