Study identifies molecular process underlying leukemia

CHAPEL HILL New research from the University of North Carolina at Chapel Hill has identified a molecular process in cells that is crucial to the development of two common leukemias. The findings help explain how fundamental cell processes go awry during cancer development and represent a first step toward new, targeted treatments for leukemia.

Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) leukemias develop when certain chromosomal abnormalities disrupt the genes that control blood cell formation. Without the proper instructions from these genes, blood cells produced by bone marrow never fully mature; these immature cells, which can't carry vital nutrients or fight infection, then flood the body.

The researchers showed how a fusion of proteins created by flawed chromosomes can trigger leukemia development. The study also identified an enzyme's important role in this process.

The results were published online Aug. 20 and will appear in a future print issue of the journal Nature Cell Biology.

The research was led by Dr. Yi Zhang, professor of biochemistry and biophysics in the UNC School of Medicine and a Howard Hughes Medical Institute Investigator. Zhang is also a member of the UNC Lineberger Comprehensive Cancer Center. The work was supported by grants from the National Institutes of Health.

The study examined chromosomal translocation, in which a fragment of a chromosome breaks off and joins another. Chromosomes are the cellular structures that carry DNA. Translocation along chromosomes can result in the generation of fusion proteins that often "misregulate" specific genes, including genes that can cause leukemia, and is a common cause of leukemia, Zhang said. The most common chromosome translocations found in leukemia patients involve the mixed lineage leukemia gene, MLL. One of the fusion proteins that partners with MLL in leukemia is AF10.

AF10 has been shown to fuse with another protein,

Contact: L.H. Lang
University of North Carolina School of Medicine

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