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CSHL team develops mouse models of leukemia that predict response to chemotherapy
Date:3/31/2009

L-triggered leukemias remained resistant and eventually killed their hosts.

The models also proved useful in helping the scientists identify the molecular basis of this difference in outcome. The chemosensitive mice with AML1/ETO-triggered leukemia had a distinct gene expression "signature" that was absent in the others; the genes whose expression was most significantly altered in the sensitive mice belong to a network controlled by p53 the gene that masterminds the cell's anti-tumor defense.

Unlike the treatment-resistant mice, the treatment-sensitive mice showed a robust activation of the p53 network. This activation was critical for a favorable outcome: when the team knocked out p53 in the chemosensitive mice, their leukemia became drug-resistant and aggressive.

"These results in the new animal models suggest that AML patients diagnosed with the MLL chromosome rearrangement will not show durable responses to standard chemotherapy," according to Lowe, Zuber, and colleagues. "These patients should be offered alternative therapeutic approaches at diagnosis."


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Contact: Hema Bashyam
bashyam@cshl.edu
516-367-6822
Cold Spring Harbor Laboratory
Source:Eurekalert

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