Activating mutations of the FLT3 receptor gene are the most common somatic mutations in AML and cause constitutive activation of the FLT3 receptor tyrosine kinase. Presence of these mutations may impact response to therapy and clinical outcome. With support of R21 funding from this PA we have made significant strides in defining the clinical significance of FLT3 mutations in AML. We propose to further delineate the biology and clinical significance of the FLT3 mutations in the upcoming pediatric and adult multi-institutional trials and more fully define a population at high-risk of relapse. In this study we will prospectively evaluate the prognostic significance of mutations of the FLT3 gene (FLT3/ITD and FLT3/ALM), FLT3J transcript levels, as well as mutations of the RTK/R/4S signal transduction pathway in multi-institutional pediatric and adult AML trials. We will further establish the role of ITD allelic ratio in FLT3/ITD population and determine the significance of the loss of heterozygosity (LOH) of 13q12 in, the pathogenesis of AML. We will also evaluate the utility of FLT3/ITD as a marker for minimal residual disease to identify patients at the highest risk of relapse. We will expand on our previous work on gene expression profiling to further identify genes that are differentially expressed in patients with FLT3 mutations and identify and validate genes involved in the pathogenesis of FLTS-mutant AML. The data generated from this study will identify AML patients at high-risk of relapse early in the course of their disease, and will be used to guide therapy in risk-based approach in future trials.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA114563-01
Application #
6911155
Study Section
Cancer Genetics Study Section (CG)
Program Officer
Thurin, Magdalena
Project Start
2005-08-01
Project End
2010-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
1
Fiscal Year
2005
Total Cost
$404,179
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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