CSHL team develops mouse models of leukemia that predict response to ch...( Cold Spring Harbor N.Y. Being able ...)

Cold Spring Harbor, N.Y. Being able to accurately predict how a given cancer will respond to chemotherapy would spare patients with non-responsive tumors the burden of undergoing toxic and ultimately unhelpful treatment. Just as important, knowing which of a patient's cancer-causing genetic lesions are contributing to drug resistance might help doctors redesign therapy for maximum benefit.

Researchers led by Professor Scott Lowe, Ph.D., of Cold Spring Harbor Laboratory (CSHL), have come closer to achieving these critical goals for human cancer therapy by developing new mouse models for human acute myeloid leukemia (AML), an aggressive and devastating cancer of white blood cells.

As Lowe and colleagues report in the April 1st issue of the journal Genes and Development, their models, which include treatment protocols that closely mimic current AML therapy in people, precisely recapitulate genetic associations that have been linked to favorable or adverse treatment responses in patients. These findings provide compelling evidence for the notion that such models can predict how human cancers will respond to therapy and help to identify genes promoting resistance or sensitivity to any cancer drug. The mouse models, the CSHL team notes, also serve as an effective test system for new drugs and treatment strategies in AML.

"By giving us a better understanding of how a cancer's genetic makeup, or 'genotype,' influences the outcomes of treatment, these models might help improve how existing drugs are used in people, and spur the design of more effective therapies," Lowe observes. "The new models are an important preclinical tool that will allow knowledge gained from cancer genetics to be put to effective use in the clinic."

The Lowe team's mouse models also provide valuable insights into how leukemia develops and progresses. Their study traces the intracellular network con
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