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Detection of Y253H BCR-ABL mutation in an imatinib resistant Chronic Myeloid Leukemia patient

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Year: 2014
COI code: CIGS13_0576
Paper Language: English

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Authors Detection of Y253H BCR-ABL mutation in an imatinib resistant Chronic Myeloid Leukemia patient

  Leili Rejali - Tehran Medical Sciences Branch – Islamic Azad University
  Behzad Poopak - Tehran Medical Sciences Branch – Islamic Azad University Payvand Clinical & Specialty Lab.
  Mandana Hasanzad - Tehran Medical Sciences Branch – Islamic Azad University
Shirin Bolouri - Payvand Clinical & Specialty Lab.

Abstract:

Chronic Myeloid Leukemia (CML) is a hematopoietic stem-cell cancer. According to WHO guideline all cases of CML carry Philadelphia chromosome or have BCR-ABL fusion gene which results from a reciprocal translocation betweenchromosomes 9 and 22. Over time, more than 50% of patients developed acquired resistance against tyrosin kinase inhibitors. Mutations in the BCR-ABL KD may contribute to imatinib resistance in CML patients. The clinical trials suggested mutational analysis of theBCR-ABL kinase domain for identification of resistance. Objectives: Analysis of BCR-ABL mutations is recommended to facilitate selection of appropriate therapy for CML patients, after treatment with imatinib has failed. Material & methods, Case Presentation: We describe a 70-year-old woman presented in 2013 with CML in accelerated phase. She was under therapy with imatinibsince five years ago (400mg daily). The main abnormal CBC parameters were thrombocytosis (PLT:1071×103cells/μl), and basophilia (24%). RNA was extracted from buffy coat and RT-PCR was done. Restriction Fragment Length Polymorphism (RFLP) for fourmutations including T315I, Y253H, E255K, M351T was performed. Results: BCR-ABL/ABL ratio determined by real-time quantitative PCR was 63.4% and the patient was classified astreatment failure according to ELN (European Leukemia Net) guideline. The three mutations T315I, E255K, M351T werenegative and Y253H mutation was detected in ABL kinase domain. Conclusion: We report Y253H mutation for the first time in Iranian imatinib resistant CML patient. Detection of ABL kinase domain mutations after imatinib resistance offers valuable information to be integrated in the subsequent therapeutic strategy

Keywords:

Y253H mutation, Chronic Myeloid Leukemia, Imatinib resistance, RealTime - PCR, RFLP

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COI code: CIGS13_0576

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Rejali, Leili; Behzad Poopak; Mandana Hasanzad & Shirin Bolouri, 2014, Detection of Y253H BCR-ABL mutation in an imatinib resistant Chronic Myeloid Leukemia patient, 12th Congress of Iranian Genetics Society, تهران, انجمن ژنتيك ايران, https://www.civilica.com/Paper-CIGS13-CIGS13_0576.htmlInside the text, wherever referred to or an achievement of this article is mentioned, after mentioning the article, inside the parental, the following specifications are written.
First Time: (Rejali, Leili; Behzad Poopak; Mandana Hasanzad & Shirin Bolouri, 2014)
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Type: Azad University
Paper No.: 547
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