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Genetic Predictive Model Based on Single Nucleotide Polymorphisms in the DNA Repair Pathway and Drug Metabolis/Transport Pharmacogenetics in the Prediction of Response and Treatment Outcomes in Acute Myeloid Leukemia

NCT01106144 · Status: UNKNOWN · Type: OBSERVATIONAL · Enrollment: 500

Last updated 2011-05-24

No results posted yet for this study

Summary

The main component in the treatment of acute myeloid leukemia (AML) is consist of anthracycline (such as daunorubicin or idarubicin) and cytarabine. Inter-individual variability of transport/metabolism of the chemotherapeutic agent and several genetic pathways involved in the drug action might be associated with different response following the treatment for AML usually consisted of chemotherapy and/or transplantation. One of potential pathways involved in the drug action is DNA repair pathway, accordingly single nucleotide polymorphisms (SNPs) in the DNA repair machinery pathway might be a predictive marker for therapy outcomes in AML.

Several genes were involved in the DNA repair machinery which are 1) Nonhomologous end joining (NHEJ) pathway involved in the G1/S phase, 2) Homologous recombinational repair (HRR) pathway involved in the S/G2 phase. XRCC4, LIG4, MRN and ATM are well known genes involved in the NHEJ pathway, while MRE11, RAD50, NBS1 (MRN), RAD51, XRCC2, XRCC3, RAD51B, RAD51C, RAD 51D, RAD52 or RAD54 are known to be associated with HRR pathway.

A study suggested that the SNPs in the DNA repair pathway was involved in the susceptibility of secondary AML developing after chemotherapy or autologous hematopoietic stem cell transplantation, thus these SNP markers could become a predictive marker for secondary AML. However, it has never been investigated for multiple candidate pathways simultaneously with relateively larger number of patients. Accordingly, the current study attempts to investigate the potential role of the genotype markers in multiple candidate pathways, esp. focused on the DNA repair machinery, with respect to response following chemotherapy or survival of AML patients.

Total of over 500 archived samples from the patients diagnosed as acute myeloid leukemia at the Samsung Medical Center, Seoul, Korea will be included, and genomic DNAs will be extracted and will be examined for their genotypes of the candidate SNPs involved in the DNA repair pathways. Then statistical analysis will be pursued for single marker analysis, haplotype analysis and for the construction of genetic risk model based on the multivariate analysis.

Conditions

  • Patients With Acute Myeloid Leukemia
  • Patients Receiving Induction/Consolidation Chemotherapy

Sponsors & Collaborators

  • Samsung Medical Center

    lead OTHER

Principal Investigators

  • Dong Hwan Kim, M.D., Ph.D. · Samsung Medical Center

Eligibility

Min Age
15 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2010-05-31

Countries

  • South Korea

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01106144 on ClinicalTrials.gov