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Exploiting WT1 Genomic Alterations for Target Identification and MRD Monitoring in Pediatric AML

Institution: 
Fred Hutchinson Cancer Research Center
Researcher(s): 
Phoenix Ho
Grant Type: 
Young Investigator Grants
Year Awarded: 
2012
Type of Childhood Cancer: 
Acute Myelogenous Leukemia (AML)
Project Description: 

AML, the second most common blood cancer in children, is a form of leukemia which is extremely difficult to treat.  Nearly half of all children diagnosed with AML will not be cured.  This includes many patients whose leukemia will initially respond to chemotherapy, only to return (or 'relapse') at a later time.  With currently available treatments, cure rates for relapsed AML remain very low.  Improved methods of predicting and detecting relapse, combined with improved leukemia treatments, are urgently needed.   It is with this in mind that our laboratory studies the WT1 gene.  WT1 plays a role in normal blood cell development; various abnormal changes in this gene are seen in leukemia cells from most pediatric AML patients.  Studying WT1 abnormalities, and understanding how these abnormalities contribute to the development of leukemia, will help us better classify AML into subtypes based on expected outcome; by predicting upfront which patients are at highest risk for relapse, we can assign treatment intensity more appropriately.  Further, we know that many extra copies of the WT1 gene are usually present in cancer cells when leukemia is first diagnosed.  We hope to prove that measuring WT1 copy numbers after chemotherapy will provide us with a method for monitoring the leukemia's response to treatment, as well as providing a suitable marker for the early detection of relapse.   Finally, we will apply this knowledge to the design of new treatments which specifically target cells with high amounts of WT1, turning this leukemia marker into a target of treatment.