Tim Pardee Lab

Understanding AML 

My lab is focused on developing a better understanding of Acute Myeloid Leukemia (AML). AML is an aggressive malignancy of the bone marrow where the white blood cells that usually protect us from infections become cancerous, leading to bone marrow failure and death. This cancer is characterized by a high relapse rate and resistance to chemotherapy. It has long been known that different genetic changes present in the leukemia cells can predict how well they will respond to therapy and how likely a patient is to achieve a lasting remission. This information is currently used to provide prognosis and direct therapy however, the mechanisms of how these genetic changes influence the way the cells respond to chemotherapy are not well understood.

To address these questions we utilize several mouse models of AML that incorporate genetic changes found in the human disease. One model uses a fusion protein found in good risk AML (AML-ETO9a) and the other a fusion from poor risk AML (MLL-ENL). These models accurately recapitulate the pathology of the disease and more importantly when mice are treated with the same chemotherapy regimes as patients the outcomes are similar. These models are based on the infection of hematopoetic stem cells with retroviruses that can be engineered to express any gene of interest. In this way different genes implicated in altering prognosis for AML patients can be incorporated into these models and their effects on chemotherapy response can be assessed.

We are currently using these models to assess how common genetic changes seen in AML effect disease onset and response to chemotherapy. The ultimate goal of this work is to better understand the mechanisms of resistance in AML and to design strategies to reverse it. Any promising findings can then be used to inform clinical trials and improve care for patients who suffer from this devastating disease.

 

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Cancer Biology

Telephone 336-716-9132

Fax 336-716-0255

E-mail
bbottoms@wakehealth.edu
Graduate Program E-mail
skridel@wakehealth.edu

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Last Updated: 04-28-2014
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