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Autophagy Does Not Contribute to TKI Response in a Imatinib-Resistant Chronic Myeloid Leukemia Cell Line

  • MOLECULAR CELL BIOLOGY
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Abstract

Autophagy is an evolutionarily conserved cellular process in which components of the cytoplasm are delivered to lysosomes for degradation and has been proposed to play a role in imatinib resistance in chronic myeloid leukemia cells. Chronic myeloid leukemia is a clonal myeloproliferative disorder arising from the neoplastic transformation of the hematopoietic stem cell. We used a Bcr-Abl-independent and imatinib-resistant K562 subpopulation (K562-IR) that we generated earlier in our laboratory for this study. We showed that in the presence of imatinib autophagy was triggered via LC3I/II transformation, p62 protein expression and acidic vacuoles accumulation in tyrosine kinase inhibitor-sensitive K562 cells; whereas in the cell line K562-IR which is imatinib-resistant and Bcr-Abl independent, autophagy is not triggered. With ongoing research and trails to combine tyrosine kinase inhibitors with autophagy inhibitors, our results suggest a model of resistance in which treatment with a TKI inhibitor does not increase autophagy, basically because its presence does not cause cellular stress due to Bcr-Abl signaling not being required for survival.

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Funding

This work is financed by Dokuz Eylul University Scientific Research Foundation grant number: 2009KBSAG29.

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Authors and Affiliations

  1. Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Inciralti-Balcova, 35340, Izmir, Turkey

    S. Baykal-Köse

  2. Dokuz Eylul University, Medical School, Medical Biology Department, 35330, Izmir, Turkey

    H. Efe & Z. Yüce

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  1. S. Baykal-Köse
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  2. H. Efe
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  3. Z. Yüce
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Contributions

Zeynep Yüce and Seda Baykal-Köse contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Seda Baykal-Köse and Hande Efe. The first draft of the manuscript was written by Seda Baykal-Köse and Zeynep Yüce. All authors read and approved the final manuscript.

Corresponding author

Correspondence to S. Baykal-Köse.

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The authors declare that they have no conflict of interest. This article does not contain any research involving humans or animals as subjects of research.

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Baykal-Köse, S., Efe, H. & Yüce, Z. Autophagy Does Not Contribute to TKI Response in a Imatinib-Resistant Chronic Myeloid Leukemia Cell Line. Mol Biol 55, 573–579 (2021). https://doi.org/10.1134/S0026893321030043

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