UNIVERSITY PARK — One sentence from a 6,500- plus word article in the medical journal Blood jumped out at Robert Paulson.

So he headed to the lab next door and handed the article to K. Sandeep Prabhu.

“Oh, wow,” Prabhu recalled saying. “We have that compound.”

The two researchers in the Penn State College of Agricultural Sciences had the same thought. “We should give this a try,” Paulson said.

A year and a half and many experiments on mice later, Paulson and Prabhu think they’ve discovered a medical breakthrough that could potentially benefit thousands of leukemia patients a year.

They’ve discovered that a compound produced from fish oil appears to not only kill certain leukemia cells in

mice but kill the stem cells that cause the cancer.

“So there seems to be no relapse. And that’s the key thing,” Paulson said in an interview last week. “And if we can translate that into the clinic, it’ll be a big breakthrough.”

There are lots of questions and experiments ahead for them. They need more funding and resources. But they’re cautiously optimistic that the treatment could work in people.

Treating all types

Scientists consider there to be four main types of leukemia, and the American Cancer Society estimates that in 2011:

• 12,950 people were diagnosed with acute myeloid leukemia (AML) and 9,050 people died from the disease.

• 14,570 were diagnosed with chronic lymphocytic leukemia (CLL) and 4,380 died from the disease.

• 5,150 were diagnosed with chronic myeloid leukemia (CML) and 270 died from the disease.

• 6,200 were diagnosed with acute lymphoblastic leukemia (ALL) and 1,420 died from the disease.

Paulson and Prabhu have had the clearest success with CML, and they published their findings in the Dec. 22 issue of Blood. They’ve also been doing experiments on AML, and they’ve described the results as promising.

“More effective therapies are urgently needed for AML patients, most of whom initially respond to standard therapies but eventually relapse,” said Deborah Banker, vice president of research communications for the Leukemia and Lymphoma Society and a former staff scientist with the Fred Hutchinson Cancer Research Center in Seattle. “And, some CML patients do not benefit (from) even the remarkable targeted drugs that are now available — they also still need better treatments.”

In the past decade, the use of certain inhibitors has increased the survival rate for patients with CML. A 2006 study by researchers from the Oregon Health & Science University Knight Cancer Institute found that patients treated with one of those inhibitors, imatinib, had a five-year survival rate of 90 percent.

But even for those who respond to the treatment, there are drawbacks. Swelling, fluid retention, rashes, nausea, muscle and bone pain, anemia and diarrhea are all common side effects of imatinib, although those conditions can sometimes be managed with other treatment. And patients often have to use the inhibitor drugs for the rest of their lives.

“Despite its impressive response rate, imatinib is rarely curative,” Dr. Robert Redner, a physician and medical researcher at the University of Pittsburgh, wrote in a study published in the February 2010 issue of The Oncologist.

But the treatment Paulson and Prabhu are pursuing would work differently.

To the source

The compound they’ve used is delta-12-protaglandin J3, or D12-PGJ3. It’s produced from a fatty acid found in fish and in fish oil, and it’s one that the human body can naturally produce.

To understand how it works, it helps to view leukemia as a pyramid.

“At the top you have a stem cell, right? And there are very few of those stem cells,” Paulson said. “And they generate a lot of leukemia cells.”

Chemotherapy drugs are essentially poisons that kill leukemia cells, along with healthy cells. But the leukemia stem cells can evade the chemotherapy treatment.

“So they just hide,” Paulson said. “And so people will go into remission as long as they’re on the drug. But as soon as they go off the drug then those stem cells just rev up again.”

But D12-PGJ3 activates a tumor suppresser gene, known as p53, inside leukemia stem cells — and that activation causes the leukemia cells to die.

“What we’re trying to do is to selectively make these stem cells, the cancer stem cells, undergo a suicidal death,” Prabhu said.

Working as a team

Paulson and Prabhu have both been at Penn State for 13 years, and they both have doctorates in biochemistry. But they bring different areas of expertise to the research.

“I come from the disease side,” said Paulson.

He’s an associate professor of veterinary and biomedical sciences, and leukemia and anemia are two of the main diseases he focuses on. His laboratory has all the charts, high-tech equipment and research assistants you’d expect, plus mouse cages — although the mice live elsewhere.

Prabhu is an associate professor of immunology and molecular toxicology. In the past, he’s studied the health benefits of compounds found in fish oil, as well as how the micronutrient selenium can curb the duplication of HIV.

His lab also has charts, high-tech equipment, research assistants that Paul-son’s lab does, plus a sticker that says: “Thank Research If ... you take medicine to treat allergies. ... you’ve never had the measles. ... you don’t know what the bubonic plague is. ... you feel great today!!!!”

The seeds of the partnership were planted at a multidisciplinary faculty lunch meeting hosted by the Huck Institutes of the Life Sciences.

Prabhu spoke about his research on the compounds from fish oil, and Paulson later connected those compounds to an article in Blood, published out of Craig Jordan’s lab at the University of Rochester.

The article focused on how a different compound, parthenolide, might destroy leukemia cells. But it also mentioned a class of compounds that Prabhu studies.

“I don’t think I would have thought about this class of compounds and their role in cancer if it hadn’t been for Sandeep,” Paulson said.

Then the experiments started.

They started trying to kill leukemia cells in petri dishes, and later they injected mice with a virus that would cause them to develop leukemia.

Then researchers injected each mouse with about 600 nanograms of D12- PGJ3 once a day for a week. And they waited.

The mice recovered, and they didn’t relapse.

Mice that didn’t receive the treatment died in eight or nine weeks. Mice that did receive the treatment in May are still alive today.

More research ahead

More experiments followed. They had the mice develop leukemia in a different way and gave them the same treatment. They got the same positive results.

They injected the compound into healthy mice. Nothing happened — which was good news. They transplanted bone marrow cells from treated mice into mice that hadn’t previously been involved in experiments.

“And they usually develop the secondary leukemia much faster. Much faster. And we did those experiments, and none of our secondary transplants developed leukemia,” Paulson said. “That was really strong evidence that we were killing the stem cells.”

That’s when they decided to publish their findings.

They’ve also applied for a patent on the compound and have other experiments planned.

They need to test the compound on human leukemia cells in a petri dish. Then they’ll want to gather mice that lack an autoimmune system, inject them with leukemia cells, and give them the same treatment. If the results are good, they can move to the clinic and human trials, which they’ve discussed with some medical institutions.

“This has been one of those great projects where we do an experiment, we get a cool result, and it immediately tells us what the next thing to do is. And we do the next experiment, and it tells us where the next one is. So we’ve just been rolling along the last few months,” said Paulson. “You rarely get on such a roll. It’s really exciting.” Prabhu agreed.

“This doesn’t happen often in science,” he said.

Ed Mahon can be reached at 231-4619.