Fatigue, abnormal bleeding, excessive bruising. Thousands of leukemia victims suffer these symptoms every day. But with a breakthrough by Michael Cosgrove, assistant professor of biology at Syracuse University, and his research team, a cure for leukemia may soon be on its way.

Cosgrove and his team found that the mixed lineage leukemia protein, an enzyme in white blood cells, works at a faster than normal pace in leukemia patients as a result of an interaction between MLL and another protein.’It works too fast, and you can’t shut it off,’ Cosgrove said. ‘We’ve devised a way to be able to shut that off. What we’re hoping to do is to find a way to turn it back down into its normal activity.’

He said he believes this can be done by adding a chemical to the cells. If that is the case, then that chemical can be made into a medicine to be administered to leukemia patients as a cure.

Cosgrove started the MLL project in 2001 while doing his postdoctoral research at Johns Hopkins University. But circumstances forced Cosgrove to put the project on the backburner, and he did not revisit his idea until 2005 when he came to SU.

His research is ongoing, and the practical effects of it may not be seen for years after more experimentation.

One of the things Cosgrove mentioned that will advance his research is the approval of pharmaceutical companies to help with clinical trials.

‘Pharmaceutical companies are looking for pipeline drugs,’ Cosgrove said. ‘A lot of the patents that they hold are running out, and they’re looking for new things to put through the assembly line.’

A drawback is that at this point, the only way to take a peptide drug is through injection, Cosgrove said.

Cosgrove is focusing on publicizing the findings to attract pharmaceutical companies to the project. He plans to contact them directly in about a year.

Cosgrove’s research had some roadblocks. He and the research team had difficulties getting the proteins to behave the way they needed them to during their research.

‘Proteins are fragile little molecules,’ Cosgrove said. ‘They require being folded in a very precise way. If it doesn’t fold properly, it doesn’t function properly. When you take it out of the cell in an isolated way, sometimes they might not fold properly.’

On the research end, the next step is identifying more interactions of the proteins, said Anamika Patel, who is conducting her postdoctoral research.

‘Suppose we have A, B, C, and D,’ Patel said. ‘We have indentified the interaction between A and B, but we have to still identify the complete thing, how B and C is formed, how C and D is formed, and how it’s overall affecting the activity of MLL.’

The team also needs to test their findings in vivo, on live tissue, before the results can be applied to medicinal use.

‘Whatever results we have are individual results,’ Patel explained. ‘We know how this functions in a test tube. This can eventually be worked out as a leukemia treatment, but the basic thing would be to test it in vivo.’

Senior biology major Benny Howard said there are many subprojects in progress under the research of MLL. He has been examining a critical structural point of the protein.

‘That’s another thing to look at when you want to design drugs,’ Howard said. ‘You can either disrupt an interaction between two proteins, or you can directly attack the protein.’

The team began the research with the intention of looking closely at the MLL protein but did not start with the intention of discovering a possible cure for leukemia. Howard said the research process was a reaction to individual discoveries.

‘In this case you said, ‘Hey, there’s something weird going on. These two proteins are doing something with each other,” he said. ”You know, I bet we can actually design a drug and disrupt this complex. Perhaps in the future this can lead to treatments that can help people with these types of leukemia.”

rhkheel@syr.edu

Published on November 11, 2008 at 12:00 pm