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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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified May 2011 by Samsung Medical Center.
Recruitment status was:  Recruiting
Information provided by:
Samsung Medical Center Identifier:
First received: April 15, 2010
Last updated: May 23, 2011
Last verified: May 2011

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.

Patients With Acute Myeloid Leukemia
Patients Receiving Induction/Consolidation Chemotherapy

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Samsung Medical Center:

Biospecimen Retention:   Samples With DNA
Preserved bone marrow sample from the adult patients with acute myeloid leukemia

Estimated Enrollment: 500
Study Start Date: May 2010
Acute myeloid leukemia


Ages Eligible for Study:   15 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Adult patients with acute myeloid leukemia receiving induction/consolidation combination chemotherapy at Samsung Medical Center from 1996 to 2005

Inclusion Criteria:

  • patients with acute myeloid leukemia
  • 15 years or older
  • patients treated with induction/consolidation chemotherapy
  • patients with available bone marrow sample

Exclusion Criteria:

  • acute biphenotypic leukemia
  Contacts and Locations
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Please refer to this study by its identifier: NCT01106144

Korea, Republic of
Samsung Medical Center IRB
Seoul, South Korea, Korea, Republic of, 135-710
Sponsors and Collaborators
Samsung Medical Center
Principal Investigator: Dong Hwan Kim, M.D., Ph.D. Samsung Medical Center
  More Information

Responsible Party: Dong Hwan Kim, Division of Hematology and Oncology/Samsung Medical Center/Sungkyunkwan University Identifier: NCT01106144     History of Changes
Other Study ID Numbers: 2008-08-094 
Study First Received: April 15, 2010
Last Updated: May 23, 2011
Health Authority: South Korea: Institutional Review Board

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms processed this record on December 09, 2016