Molecular screening and the clinical impacts of BCR‑ABL KD mutations in patients with imatinib‑resistant chronic myeloid leukemia

  • Authors:
    • Betül Koçkan
    • Tayfur Toptaş
    • Işik Atagündüz
    • Ayşe Tülin Tuğlular
    • Ayşe Özer
    • Mustafa Akkiprik
  • View Affiliations

  • Published online on: December 13, 2017     https://doi.org/10.3892/ol.2017.7606
  • Pages:2419-2424
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Abstract

The present study aimed to detect the frequency of kinase domain (KD) mutations in order to evaluate their clinical significance and functional importance in 45 patients with chronic myeloid leukemia (CML) who were resistant to imatinib therapy. Sanger sequencing was used (45 patients), along with allele‑specific oligonucleotide polymerase chain reaction (ASO‑PCR; 3 patients), for the screening of mutations. BCR/ABL KD was amplified by nested PCR and sequencing was performed. Secondly, ASO‑PCR was performed to confirm the results of the sequence analysis for E255K mutations. Mutations were detected in 11/45 patients (24.44%) via Sanger sequencing. D241G (4.4%), C369C (4.4%), K285N (2.2%), A380T (2.2%) and A366V (2.2%) mutations were detected. E255K (8.8%) was detected by ASO‑PCR and Sanger sequencing. Mutations are a primary reason for suboptimal responses, loss of response and resistance to imatinib. In particular, the E255K mutation, which is characterized by resistance to imatinib and nilotinib, was detected in four patients. Analyzing the mutations and monitoring patients with CML may improve their prognosis and survival rate. ASO‑PCR assays will be beneficial for the routine monitoring of mutations.

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February 2018
Volume 15 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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APA
Koçkan, B., Toptaş, T., Atagündüz, I., Tuğlular, A.T., Özer, A., & Akkiprik, M. (2018). Molecular screening and the clinical impacts of BCR‑ABL KD mutations in patients with imatinib‑resistant chronic myeloid leukemia. Oncology Letters, 15, 2419-2424. https://doi.org/10.3892/ol.2017.7606
MLA
Koçkan, B., Toptaş, T., Atagündüz, I., Tuğlular, A. T., Özer, A., Akkiprik, M."Molecular screening and the clinical impacts of BCR‑ABL KD mutations in patients with imatinib‑resistant chronic myeloid leukemia". Oncology Letters 15.2 (2018): 2419-2424.
Chicago
Koçkan, B., Toptaş, T., Atagündüz, I., Tuğlular, A. T., Özer, A., Akkiprik, M."Molecular screening and the clinical impacts of BCR‑ABL KD mutations in patients with imatinib‑resistant chronic myeloid leukemia". Oncology Letters 15, no. 2 (2018): 2419-2424. https://doi.org/10.3892/ol.2017.7606