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Genome-wide mouse study yields link to human leukemia

Thanks to a handful of very special mice, scientists have discovered a new tumor suppressor gene and a unique chemical signature implicated in the development of human leukemia, findings that open up a "treasure box" of opportunity and possibility, study authors say.

Researchers in The Ohio State University Comprehensive Cancer Center bred a type of mouse that develops acute lymphoblastic leukemia (ALL). The mouse first goes through a pre-leukemic stage marked by rapidly expanding T cells and natural killer cells, both major components of the immune system.

In comparing the mice in the pre-leukemic stage and those with ALL with normal mice, researchers found that methylation, a chemical process that adds methyl molecules to DNA, silenced a number of genes ?but only in the mice with full-blown ALL.

Further tests revealed that the methylation pattern in the mice with leukemia is strikingly similar to the pattern of methylation in human leukemia.

In the process, the researchers also identified a new gene that when methylated, appears to interrupt normal cell death, a process called apoptosis.

"It's given us a whole new way to look at and possibly treat leukemia," says Michael Caligiuri, director of the OSU Comprehensive Cancer Center (OSUCCC) and senior co-author of the study. "It's also validated our mouse model as a good predictor of what happens in the development of human disease," he added.

The findings appear in Nature Genetics online at http://www.nature.com/ng/.

"This is the first time anyone has examined methylation in leukemia on a genome-wide basis in a mouse, and the findings offer important implications for patient care, since we know that methylation, which alters gene function, can be reversed," says Christoph Plass, senior co-author and a member of the OSUCCC's Molecular Biology and Cancer Genetics and Experimental Therapeutics Programs.

While it was Caligiuri's laboratory that designed the
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Source:Ohio State University


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