Mouse strain with gene stutter will help leukemia research

COLUMBUS, Ohio Cancer researchers have developed a new strain of mice that should help reveal how an unusual change in a certain gene contributes to a particularly deadly form of acute myeloid leukemia (AML).

A study of the strain by its developers at the Ohio State University Comprehensive Cancer Center (OSUCCC) suggests that the genetic change comes early in the disease, and that it over-activates a second gene that helps govern blood cell development.

The genetic change, known as a partial tandem duplication, is located in a gene called MLL (for mixed-lineage leukemia). A partial tandem duplication is a type of gene mutation that occurs when a section of a gene is repeated, like a stutter in the gene's DNA.

The new mouse model should help leukemia researchers to learn how this mutation contributes to AML development, and it may lead to new ways to treat, diagnose and perhaps prevent the disease.

The findings were published online Sept. 14 in the Journal of Clinical Investigation.

"When leukemia strikes, it's like a hurricane arriving without an advance weather forecast you have no information about how it got there, and it's a level-5 storm," says Michael A. Caligiuri, principal investigator of the study and director of the OSUCCC.

"Studying live models like this mouse strain helps us begin to understand the earliest events in the development of leukemia. This in turn will someday allow us to understand what causes leukemia in people, predict who is at greatest risk and prevent leukemia from ever developing in those patients."

Genes store information for a protein. Mutations can alter the protein, perhaps making it function differently. In this case, the duplication within the MLL gene contributes to an aggressive form of AML. This new study begins to reveal how it does so.

AML will strike an estimated 10,000 Americans this year, and about 45 percent of those will have cancer cel

Contact: Darrell E. Ward
Ohio State University

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