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Syracuse University researchers discover new way to attack some forms of leukemia
Date:10/28/2008

a basketball without it tangling or breaking," Cosgrove says. What differentiates a liver cell from a blood cell is how that DNA is compacted or packaged in the cell nuclei, which results in different genes being expressed and leads to the production of specialized cells (white blood cells, liver cells, pancreatic cells, etc.). Proteins control this DNA packaging process.

Cosgrove's research team has spent the past three years studying one of the proteins that regulate the way DNA is packaged when white blood cells are formed. The protein is called the Mixed Lineage Leukemia (MLL) protein. In normal cells, the MLL protein, which contains 3,969 amino acids, combines with three other proteins to create a molecular switch that controls the DNA packaging events required for the formation of white blood cells. In some types of leukemia, the MLL switch is broken, which prevents white blood cells from maturing properly, resulting in a dangerous proliferation of immature white blood cells.

Cosgrove's team identified a tiny component of the MLL proteina peptide sequence that contains just six amino acidsthat is responsible for assembling the MLL molecular switch in normal cells. The team members called this peptide sequence the "Win" motif. They discovered that a synthetic version of this peptide acts like a drug that breaks apart the MLL molecular switch, interrupting a critical enzymatic process that is required to produce white blood cells. When used against an MLL molecular switch that is brokenworking too fastthe peptide drug attacks the protein switch and breaks it apart, which may slow or stop the production of the abnormal white blood cells. This drug may help to reprogram the way DNA is packaged in leukemia cells and help convert the abnormal cells back into normal cells.

"Reprogramming the way DNA is packaged in cancerous cells is a new idea that has the potential to lead to better treatments with fewer side effects," Cosgrove says.
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Contact: Judy Holmes
jlholmes@syr.edu
315-443-8085
Syracuse University
Source:Eurekalert

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