Frequency of T۳۱۵I Mutation in Patients with Chronic Myeloid Leukemia Before and During Imatinib Treatment: A Study in North-East of Iran

  • سال انتشار: 1402
  • محل انتشار: مجله علمی پژوهشی دانشگاه علوم پزشکی زنجان، دوره: 31، شماره: 146
  • کد COI اختصاصی: JR_ZUMS-31-146_005
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 122
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نویسندگان

Omalbanin Mokhlesi

Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Mohammad Hadi Sadeghian

Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Arezoo Shajiei

Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Maryam Sheikhi

Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Payam Siyadat

Dept. of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran

Mohammad Mehdi Kooshyar

School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Hossein Rahimi

School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Nafiseh Amini

Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Maliheh Dadgar Moghadam

School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Hossein Ayatollahi

Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Seyyede Fatemeh Shams

Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Zahra Khoshnegah

Dept. of Hematology and Blood Banking, Faculty of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran

چکیده

Background and Objective: Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by an aberrant BCR-ABL fusion protein. Imatinib mesylate (IM) is a tyrosine kinase inhibitor that induces clinical remissions in chronic-phase CML patients. The T۳۱۵I mutation at the gatekeeper residues of BCR-ABL confers resistance to both IM and second-generation TKIs, including dasatinib and nilotinib. Our objective was to determine the prevalence of T۳۱۵I mutation between two groups of CML patients before and during Imatinib treatment in North-East of Iran. Materials and Methods: This study was conducted on ۱۰۰ newly diagnosed cases of CML (before commencing IM treatment) and ۲۵ IM-resistant CML patients. PCR-RFLP, ASO-PCR, and direct sequencing were performed to detect T۳۱۵I mutations. Results: The median age of newly-diagnosed and IM-resistant patients was ۴۸±۱۴ and ۵۰±۱۲.۳ years, respectively. Males/Females ratio was ۱ and ۱.۰۸ for newly diagnosed and IM-resistant patients, respectively. There was no significant difference regarding the age and sex between the two groups. During the study, T۳۱۵I mutational analysis was performed for all ۱۲۵ patients. The prevalence of T۳۱۵I mutation was ۰% and ۴% for newly-diagnosed and IM-resistant patients, respectively. T۳۱۵I mutation was not detected before IM administration, although it was detected in ۱ (۴%) among resistant patients who were at least ۶-months on IM treatment. Conclusion: These observations suggest that T۳۱۵I mutation may be categorized as secondary resistance and induce clonal expansion due to BCR/ABL instability. Hence, BCR-ABL mutations are less likely to appear before the onset of treatment, as presented in our study.

کلیدواژه ها

T۳۱۵I Mutation, Chronic Myeloid Leukemia (CML), Imatinib Resistance

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