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CSHL scientists reveal mechanism behind 'oncogene addiction' in acute leukemia
Date:7/31/2011

Cold Spring Harbor, NY A team of scientists at Cold Spring Harbor Laboratory (CSHL) has laid bare the mechanism behind a phenomenon called oncogene addiction in mice suffering from a form of leukemia that mimics acute myelogenous leukemia (AML) in humans. Significantly, the team was able to mobilize their newly gained understanding to target "addiction" pathways in the model mice, resulting in rapid and complete eradication of the cancer, which is usually fatal and resistant to conventional chemotherapy.

Oncogene addiction refers to the curious phenomenon that cancer cells, despite harboring many genetic alterations, can remain dependent on the continuing expression of a single aberrant, cancer-promoting gene an oncogene. In this case, the gene in question, called MLL, has long been implicated in human cancers of the blood. In AML, as a result of a genetic anomaly, the protein expressed by the MLL gene fuses with another protein, to form a fusion oncoprotein called MLL-AF9. It is this protein to which AML cancer cells are "addicted."

"The crucial questions are what MLL-AF9 enables cancer cells to do, and how we might intervene to suppress these effects in other words, how to use our knowledge of the mechanism behind the cancer cell's addiction for developing highly specific anti-cancer therapies.," says CSHL Adjunct Professor and HHMI Investigator Scott W. Lowe, who directed the research, which is reported in a paper that appears August 1 in the journal Genes & Development. "Until now, we've not been able to answer these questions in living animals."

The team's research demonstrated that MLL-AF9 enforces a cellular program that enables blood cells to keep renewing themselves, rather than progressing through the usual stages of cellular life, and eventually dying. While this property of aberrant self-renewal has been a known characteristic of leukemia cells for many years, Lowe and his CSHL colleagues were able to decip
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Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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