ON LITTLE MORE THAN A WHIM, TWO PENN STATE RESEARCHERS DECIDED
TO SEE WHAT A COMMON COMPOUND WOULD DO TO LEUKEMIA CELLS. THEY WERE SHOCKED BY THE RESULT: A POSSIBLE CURE FOR LEUKEMIA.
TO SEE WHAT A COMMON COMPOUND WOULD DO TO LEUKEMIA CELLS. THEY WERE SHOCKED BY THE RESULT: A POSSIBLE CURE FOR LEUKEMIA.
llustration by Wayne Brezinka
Within 24 hours, they had all committed suicide. Or what at least approximates suicide. Scientists call it apoptosis, and it’s what happened in Room104 Henning Building one summer day in 2010. The sun was shining. The birds were singing. And 500,000 leukemia cells were heading to the big Petri dish in the sky.
The day before, Robert Paulson and Sandeep Prabhu, two veterinary and biomedical sciences researchers, had decided to dribble a few drops of a compound called D12-PGJ3 into leukemia cell cultures to see how the cells reacted.
Their labs had been adjacent for years, but Paulson, whose specialty is leukemia stem cells, and Prabhu, an expert on fatty acid derivatives, never had reason to cross pollinate their research until an article in the journal Blood prompted them to try this new experiment.
To their surprise, the experiment resulted in apoptosis—a process by which cells voluntarily shut down, effectively killing themselves, when they know they’re no longer needed. At the time, the initial results were simply unexpected. Now, after subsequent rounds of testing, Paulson and Prabhu have discovered that D12-PGJ3 may be a cure for certain types of leukemia.
Existing treatments for leukemia are just that—treatments. Paulson and Prabhu’s compound may actually prevent the disease and protect people against relapse. “There are no drugs that target leukemia stem cells right now, and that’s a major question in the field—how can we do that?” says Paulson. “Our compound works so well, and that’s what really has us excited.”
D12-PGJ3 is short for delta-12-prostaglandin J3. And it turns out it’s been right under our noses for quite a while. The compound is derived from omega-3 fatty acids in fish oil, the same fish oil many people use as a nutritional supplement to keep their cholesterol in check.
Over the past 18 months, Paulson and Prabhu have expanded the use of D12-PGJ3 beyond cell cultures in a Petri dish to mice. With graduate assistants Shailaja Hegde and Ujjawal Gandhi, and post-doctoral fellows Naveen Kaushal, Chris Chiaro, and Kodilhalli Ravindra, they re-tooled the doses, eventually learning that even at miniscule amounts, the compound can trick both normal leukemia cells and leukemia stem cells—the cells that cause and spread the disease—into undergoing apoptosis.
That the compound works in such small doses (as small as 10-9 molar, to be exact) could reduce the amount and severity of potential side effects—another advantage over existing leukemia treatments.
What’s more, the team’s experiments with mice have been exceptionally promising: Every single mouse treated with the compound was cured of leukemia and resistant to relapse. Such sweeping positive results are rare in any scientific experiment, let alone those that have such high potential public impact.
“We can say with confidence that, yes, we have cured leukemia,” Prabhu says, “but at this point it’s only in mice.”
The next step is to test D12-PGJ3 on human leukemia cell cultures, and then on actual human leukemia patients. The biggest obstacle is funding.
Among the four major types of leukemia—chronic myelogenous leukemia (CML), acute myeloid leu-kemia (AML), chronic lymphocytic leukemia (CLL), and acute lympho-cytic leukemia (ALL)—Paulson and Prabhu have published their findings only on CML. (The paper appeared in the Dec. 22 issue of Blood.)
But Prabhu says further testing has already shown similar results with AML, and they’re continuing more tests on the other types, as well as tests to figure out the exact chemical mechanism for how D12-PGJ3 works.
“We have high hopes that this could be much more broad-based than CML,” Paulson agrees. “To be able to have something actually make it into the clinic would just be incredible. I can’t even describe how cool that would be.”