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ABL1 tyrosine kinase domain mutations in chronic myeloid leukemia treatment resistance

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Abstract

The development of mutations in the BCR-ABL1 fusion gene transcript causes resistance to tyrosine kinase inhibitors (TKIs) based therapy in chronic myeloid leukemia (CML). Thereby, screening for BCR-ABL1 mutations is advised especially in patients undergoing poor response to treatment. In the current study the authors investigated 43 patients with CML that failed or had suboptimal response to TKIs treatment. Blood samples were collected from patients that were treated with TKIs. The analysis of genetic mutations was performed using a semi-nested PCR assay, followed by Sanger sequencing. The analysis revealed 15 mutations (32.55%): 14 point mutations and an exon 7 deletion. In roughly 30% of cases, mutations in the BCR-ABL1 fusion gene are common causes for treatment resistance.

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Authors and Affiliations

  1. Department of Molecular Genetics, Research Center Transcend, Regional Institute of Oncology, General Henri Mathias Berthelot Street, No. 2-4, 700483, Iasi, Romania

    Irina Cezara Vacarean-Trandafir, Iuliu Cristian Ivanov & Loredana Mihaiela Dragos

  2. Department of Molecular Genetics and Biochemistry, “Alexandru Ioan Cuza” University, Carol I Bd., No. 11, 700506, Iasi, Romania

    Irina Cezara Vacarean-Trandafir, Loredana Mihaiela Dragos & Dumitru Cojocaru

  3. Department of Hematology, Regional Institute of Oncology, General Henri Mathias Berthelot Street, No. 2-4, 700483, Iasi, Romania

    Angela Smaranda Dascalescu & Amalia Andrea Titieanu

  4. Department of Physiopathology, Grigore T. Popa University of Medicine and Pharmacy, Universitatii Street, No. 16, 700115, Iasi, Romania

    Amalia Andrea Titieanu

  5. Academy of Romanian Scientists, Splaiul Independentei Street, No. 54, 050094, Bucharest, Romania

    Dumitru Cojocaru

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  1. Irina Cezara Vacarean-Trandafir
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Correspondence to Irina Cezara Vacarean-Trandafir.

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Vacarean-Trandafir, I.C., Ivanov, I.C., Dragos, L.M. et al. ABL1 tyrosine kinase domain mutations in chronic myeloid leukemia treatment resistance. Mol Biol Rep 46, 3747–3754 (2019). https://doi.org/10.1007/s11033-019-04816-5

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