Patients Receiving Induction/Consolidation Chemotherapy Clinical Trial
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
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.
n/a
Observational Model: Case-Only, Time Perspective: Retrospective