title: Low level of TERC gene amplification between chronic myeloid leukaemia patients resistant and respond to imatinib mesylate treatment.
abstract: The amplification of telomerase component (TERC) gene could play an important role in generation and treatment of haematological malignancies. This present study was aimed to investigate copy number amplification status of TERC gene in chronic myeloid leukaemia (CML) patients who were being treated with imatinib mesylate (IM). Genomic DNA was extracted from peripheral blood of CML-IM Resistant (n=63), CML-IM Respond (n=63) and healthy individuals (n=30). TERC gene copy number predicted (CNP) and copy number calculated (CNC) were determined based on Taqman® Copy Number Assay. Fluorescence in situ hybridization (FISH) analysis was performed to confirm the normal signal pattern in C4 (calibrator) for TERC gene. Nine of CML patients showed TERC gene amplification (CNP=3), others had 2 CNP. A total of 17 CML patients expressed CNC>2.31 and the rest had 2.31>CNC>1.5. TERC gene CNP value in healthy individuals was 2 and their CNC value showed in range 1.59-2.31. The average CNC TERC gene copy number was 2.07, 1.99 and 1.94 in CML- IM Resistant patients, CML-IM Respond and healthy groups, respectively. No significant difference of TERC gene amplification observed between CML-IM Resistant and CML-IM Respond patients. Low levels of TERC gene amplification might not have a huge impact in haematological disorders especially in terms of resistance towards IM treatment.
authors.affiliation: Human Genome Center, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia E-mail : ssarina@kck.usm.my.
authors.forename: Zaidatul Shakila
authors.initials: ZS
authors.lastname: Mohamad Ashari
authors.forename: Sarina
authors.initials: S
authors.lastname: Sulong
authors.forename: Rosline
authors.initials: R
authors.lastname: Hassan
authors.forename: Azlan
authors.initials: A
authors.lastname: Husin
authors.forename: Goh Ai
authors.initials: GA
authors.lastname: Sim
authors.forename: S Fadilah
authors.initials: SF
authors.lastname: Abdul Wahid
mesh_terms: D001549:Benzamides / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D056915:DNA Copy Number Variations; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005784:Gene Amplification / Q000235:genetics*; D018628:Gene Dosage / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012313:RNA / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; C422952:telomerase RNA; D012313:RNA; D000068877:Imatinib Mesylate; D019098:Telomerase