Vol 55(2021) N 4 p. 573-579; DOI 10.1134/S0026893321030043
S. Baykal-Köse1*, H. Efe2, Z. Yüce2
Autophagy Does Not Contribute to TKI Response in a Imatinib-resistant Chronic Myeloid Leukemia Cell Line#1Izmir Biomedicine and Genome Center (IB G), Dokuz Eylul University Health Campus, Inciralti-Balcova, Izmir, 35340 Turkey
2Dokuz Eylul University, Medical School, Medical Biology Department, Izmir, 35330 Turkey
Received - 2020-06-30; Revised - 2020-08-27; Accepted - 2020-09-03
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.
autophagy, chronic myeloid leukemia, imatinib, CML, TKI resistance