en Medical Biology Medical Biology مقاله پژوهشی Original Research Article <p style="text-align: justify;"><span style="font-size:16px;"><span style="font-family:Times New Roman;"><strong new="" roman="" style="font-family: " times=""><span style="color:#ffffff;"><span style="background-color:#16a085;">Background and Objective:</span></span>&nbsp;</strong><span style="line-height:150%"><span style="line-height:150%">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 T315I mutation at the gatekeeper residues of BCR-ABL confers resistance to both IM and second-generation TKIs, including dasatinib and nilotinib. </span>Our <span style="line-height:150%">objective was to determine the prevalence of T315I mutation between two groups of CML patients before and during Imatinib treatment in North-East of Iran.</span></span><br> <strong new="" roman="" style="font-family: " times=""><span style="color:#ffffff;"><span style="background-color:#16a085;">Materials and Methods:</span></span>&nbsp;</strong><span style="line-height:150%"><span style="line-height:150%">This study was conducted on 100 newly diagnosed cases of CML (before commencing IM treatment) and 25 IM-resistant CML patients. PCR-RFLP, ASO-PCR, and direct sequencing were performed to detect T315I mutations.</span></span><br> <strong new="" roman="" style="font-family: " times=""><span style="color:#ffffff;"><span style="background-color:#16a085;">Results:</span></span></strong>&nbsp;<span style="line-height:150%"><span style="line-height:150%">The median age of newly-diagnosed and IM-resistant patients was 48&plusmn;14 and 50&plusmn;12.3 years, respectively. Males/Females ratio was 1 and 1.08 for newly diagnosed and IM</span>-<span style="line-height:150%">resistant patients, respectively. There was no significant difference regarding the age and sex between the two groups. During the study, T315I mutational analysis was performed for all 125 patients. The prevalence of T315I mutation was 0% and 4% for newly-diagnosed and IM-resistant patients, respectively. T315I mutation was not detected before IM administration, although it was detected in 1 (4%) among </span>resistant patients who <span style="line-height:150%">were at least 6-months on IM treatment.</span></span><br> <strong new="" roman="" style="font-family: " times=""><span style="color:#ffffff;"><span style="background-color:#16a085;">Conclusion:</span></span>&nbsp;</strong><span style="line-height:150%"><span style="line-height:150%">These observations suggest that T315I 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.</span></span></span></span></p> T315I Mutation, Chronic Myeloid Leukemia (CML), Imatinib Resistance 244 249 http://journal.zums.ac.ir/browse.php?a_code=A-10-6273-1&slc_lang=en&sid=1 Omalbanin Mokhlesi mokhlesio2@mums.ac.ir 5200319475328460076718 5200319475328460076718 No Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Mohammad Hadi Sadeghian sadeghianmh@mums.ac.ir 5200319475328460076719 5200319475328460076719 No Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Arezoo Shajiei arezoo.shajiei@gmail.com 5200319475328460076720 5200319475328460076720 No Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Maryam Sheikhi sheikhim75@gmail.com 5200319475328460076721 5200319475328460076721 No Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Payam Siyadat payam.siyadat19899@gmail.com 5200319475328460076722 5200319475328460076722 No Dept. of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran Mohammad Mehdi Kooshyar kooshyarmm@mums.ac.ir 5200319475328460076723 5200319475328460076723 No School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Hossein Rahimi rahimih@mums.ac.ir 5200319475328460076724 5200319475328460076724 No School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Nafiseh Amini aminin3@mums.ac.ir 5200319475328460076725 5200319475328460076725 No Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Maliheh Dadgar Moghadam moghadammd@mums.ac.ir 5200319475328460076726 5200319475328460076726 No School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Hossein Ayatollahi ayatollahih@mums.ac.ir 5200319475328460076727 5200319475328460076727 Yes Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Seyyede Fatemeh Shams shams8869@yahoo.com 5200319475328460076728 5200319475328460076728 No Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Zahra Khoshnegah zkhoshnegah@gmail.com 5200319475328460076729 5200319475328460076729 No Dept. of Hematology and Blood Banking, Faculty of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran