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

Baykal-Kose S., Efe H., Yuce Z.

MOLECULAR BIOLOGY, vol.55, no.4, pp.573-579, 2021 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 55 Issue: 4
  • Publication Date: 2021
  • Doi Number: 10.1134/s0026893321030043
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Veterinary Science Database
  • Page Numbers: pp.573-579
  • Keywords: autophagy, chronic myeloid leukemia, imatinib, CML, TKI resistance, SURVIVAL REGULATION, MOLECULAR-BIOLOGY, TARGETED THERAPY, DEATH, INHIBITOR
  • Dokuz Eylül University Affiliated: Yes


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.