Identification of DNA methylation biomarkers in imatinib-resistant chronic myeloid leukemia cells

Ren In You, Ching Liang Ho, Hsiu Man Hung, Yu Fung Hsieh, Jy Ciou Ju, Tsu Yi Chao

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Drug resistance is an obstacle to successful cancer treatment. In hematological neoplasms, such as chronic myelogenous leukemia (CML), drug resistance is often associated with gene hypermethylation and loss of function. An imatinib-resistant subclone of CML-like K562 (K562-R) was used as a model to study the role of hypermethylation in drug resistance. K562-R was selected by culturing cells with increasing concentrations of imatinib, ranging from 0.2-5 μM. A DNA methylation microarray was performed on the K562-R and parental K562 cells, and selected gene expression levels were confirmed using real-time polymerase chain reaction. The methylation level was significantly increased and the gene expression level significantly was decreased for MLH1, RPRM, FEM1B, and THAP2 in K562-R cells compared with parental K562 cells. Exposing K562-R cells to methylation inhibitors, such as 5-azacytidine (AzaC) and trichostatin A (TSA), reduced imatinib resistance. Our approach of using a drug-limiting dilution model followed by the use of a methylation microarray was able to identify methylation biomarkers for drug resistance. Specifically, MLH1, RPRM, FEM1B, and THAP2 might be potential epigenetic targets of imatinib resistance. Further understanding the methylation domain and epigenetic regulation machinery of these biomarkers will help researchers find potential effective therapeutic strategies that could be used to overcome drug resistance in CML patients.

Original languageEnglish
Pages (from-to)12-15
Number of pages4
JournalGenomic Medicine, Biomarkers, and Health Sciences
Volume4
Issue number1-2
DOIs
Publication statusPublished - Mar 2012

Fingerprint

Methylation
Biomarkers
Myeloid Cells
DNA Methylation
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Drug Resistance
K562 Cells
Pharmaceutical Preparations
Microarrays
Epigenomics
Gene expression
trichostatin A
Gene Expression
Azacitidine
Oncology
Polymerase chain reaction
Hematologic Neoplasms
Oligonucleotide Array Sequence Analysis
Dilution
Machinery

Keywords

  • Chronic myeloid leukemia
  • Imatinib-resistant
  • Methylation biomarkers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biomedical Engineering
  • Medicine(all)
  • Drug Discovery

Cite this

Identification of DNA methylation biomarkers in imatinib-resistant chronic myeloid leukemia cells. / You, Ren In; Ho, Ching Liang; Hung, Hsiu Man; Hsieh, Yu Fung; Ju, Jy Ciou; Chao, Tsu Yi.

In: Genomic Medicine, Biomarkers, and Health Sciences, Vol. 4, No. 1-2, 03.2012, p. 12-15.

Research output: Contribution to journalArticle

You, Ren In ; Ho, Ching Liang ; Hung, Hsiu Man ; Hsieh, Yu Fung ; Ju, Jy Ciou ; Chao, Tsu Yi. / Identification of DNA methylation biomarkers in imatinib-resistant chronic myeloid leukemia cells. In: Genomic Medicine, Biomarkers, and Health Sciences. 2012 ; Vol. 4, No. 1-2. pp. 12-15.
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