Grant Number:	1R01CA133881-01A2 Interpret this number
Primary Investigator:	Aplenc, Richard
Organization:	Children'S Hosp Of Philadelphia
Project Title:	Genetic Predictors of Aml Treatment Response
Fiscal Year:	2010

DESCRIPTION (provided by applicant): Although acute myeloid leukemia (AML) causes substantial treatment burden in both children and adults, AML treatment response remains incompletely understood. This application proposes a genome-wide association study (GWAS) of pediatric AML treatment response. Two hypotheses underlie this application. First, somatic genetic variation will modify AML relapse and treatment related infection risk. Second, clinical trial simulations (CTS) may define how genetic variation data may be used to modify AML treatment. These hypotheses will be tested in three specific aims. Aim 1 will use the Illumina Human 610 HH Bead Chip to perform a GWAS with 840 patients to identify genotypes associated with AML relapse and infectious complication risk. Aim 2 will use the Illumina Infinium" Chip to validate 4% of SNPs found in Aim 1 in 1,160 Caucasian patients and 750 non-Caucasian patients. Aim 3 will use CTS to test the clinical applicability of infection susceptibility genotypes discovered and validated in the first two aims. This application has significance both as the first GWAS in AML and as a novel step towards translating genetic variability data into the clinical care of patients. Furthermore, since pediatric and adult AML share common molecular pathologies and treatment strategies, this research may inform the care of both adult and pediatric AML patients. PUBLIC HEALTH RELEVANCE: Acute myeloid leukemia (AML) causes a substantial disease and treatment burden in both children and adults. This application will provide data on the role of somatic genetic variability in AML treatment response and will use clinical trial simulations to model the application of genotype data to clinical patient care. Thus, this application may not only inform the care of adult and pediatric AML patients, but may also provide important insights into the translation of genotype data into patient care.




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ABCB1 SNP predicts outcome in patients with acute myeloid leukemia treated with Gemtuzumab ozogamicin: a report from Children's Oncology Group AAML0531 Trial.
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Successful merging of data from the United Network for Organ Sharing and the Pediatric Health Information System databases.
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The epidemiology of rasburicase use in paediatric patients with acute lymphoblastic leukaemia and non-Hodgkin lymphoma.
Authors: Citrin R. , Getz K.D. , Li Y. , Huang Y.S. , Horowitz J.P. , Seif A.E. , Fisher B.T. , Aplenc R. .
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CD33 splicing SNP regulates expression levels of CD33 in normal regenerating monocytes in AML patients.
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CD33 Splicing Polymorphism Determines Gemtuzumab Ozogamicin Response in De Novo Acute Myeloid Leukemia: Report From Randomized Phase III Children's Oncology Group Trial AAML0531.
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Genomic architecture and treatment outcome in pediatric acute myeloid leukemia: a Children's Oncology Group report.
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Creation of a pediatric mature B-cell non-Hodgkin lymphoma cohort within the Pediatric Health Information System Database.
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Concordance of copy number alterations using a common analytic pipeline for genome-wide analysis of Illumina and Affymetrix genotyping data: a report from the Children's Oncology Group.
Authors: Vujkovic M. , Attiyeh E.F. , Ries R.E. , Horn M. , Goodman E.K. , Ding Y. , Kavcic M. , Alonzo T.A. , Gerbing R.B. , Hirsch B. , et al. .
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Dexrazoxane exposure and risk of secondary acute myeloid leukemia in pediatric oncology patients.
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Variation in Risk of Hospital-Onset Clostridium difficile Infection Across ß-Lactam Antibiotics in Children With New-Onset Acute Lymphoblastic Leukemia.
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TPMT and MTHFR genotype is not associated with altered risk of thioguanine-related sinusoidal obstruction syndrome in pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group.
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Patient and hospital factors associated with induction mortality in acute lymphoblastic leukemia.
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Antifungal prophylaxis associated with decreased induction mortality rates and resources utilized in children with new-onset acute myeloid leukemia.
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Risk factors for renal failure in pediatric patients with acute myeloid leukemia: a retrospective cohort study.
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