Adaptive phenotypic modulations lead to therapy resistance in chronic myeloid leukemia cells

Baykal-Köse, Seda and Acikgoz, Eda and Yavuz, Ahmet Sinan and Geyik, Öykü Gönül and Ateş, Halil and Sezerman, Osman Uğur and Özsan, Güner Hayri and Yüce, Zeynep (2020) Adaptive phenotypic modulations lead to therapy resistance in chronic myeloid leukemia cells. PLoS ONE, 15 (2). ISSN 1932-6203

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Tyrosine kinase inhibitor (TKI) resistance is a major problem in chronic myeloid leukemia (CML). We generated a TKI-resistant K562 sub-population, K562-IR, under selective imatinib-mesylate pressure. K562-IR cells are CD34-/CD38-, BCR-Abl-independent, proliferate slowly, highly adherent and form intact tumor spheroids. Loss of CD45 and other hematopoietic markers reveal these cells have diverged from their hematopoietic origin. CD34 negativity, high expression of E-cadherin and CD44; decreased levels of CD45 and β-catenin do not fully confer with the leukemic stem cell (LSC) phenotype. Expression analyses reveal that K562-IR cells differentially express tissue/organ development and differentiation genes. Our data suggest that the observed phenotypic shift is an adaptive process rendering cells under TKI stress to become oncogene independent. Cells develop transcriptional instability in search for a gene expression framework suitable for new environmental stresses, resulting in an adaptive phenotypic shift in which some cells partially display LSC-like properties. With leukemic/cancer stem cell targeted therapies underway, the difference between treating an entity and a spectrum of dynamic cellular states will have conclusive effects on the outcome.
Item Type: Article
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Ahmet Sinan Yavuz
Date Deposited: 31 Jul 2023 21:58
Last Modified: 31 Jul 2023 21:58

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