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Adaptive Phenotypic Modulations Lead To Therapy Resistance in Chronic Myeloid Leukemia Cells

dc.authorid Yuce, Zeynep/0000-0002-2762-0942
dc.authorid Yavuz, Ahmet Sinan/0000-0003-4069-6105
dc.authorid Baykal, Seda/0000-0001-8654-5332
dc.authorid Acikgoz, Eda/0000-0002-6772-3081
dc.authorid Gonul Geyik, Oyku/0000-0003-3014-1253
dc.authorid Sezerman, Osman Ugur/0000-0003-0905-6783
dc.authorscopusid 57215183798
dc.authorscopusid 56364984200
dc.authorscopusid 38663627200
dc.authorscopusid 57221379876
dc.authorscopusid 36839384300
dc.authorscopusid 57195305621
dc.authorscopusid 35619464700
dc.authorwosid Gönül Geyi̇k, Öykü/Ahb-4716-2022
dc.authorwosid Yuce, Zeynep/Jdw-8153-2023
dc.authorwosid Baykal, Seda/Abi-4548-2020
dc.authorwosid Acikgoz, Eda/W-2171-2017
dc.authorwosid Sezerman, Osman/X-6441-2018
dc.contributor.author Baykal-Kose, Seda
dc.contributor.author Acikgoz, Eda
dc.contributor.author Yavuz, Ahmet Sinan
dc.contributor.author Geyik, Oyku Gonul
dc.contributor.author Ate, Halil
dc.contributor.author Sezerman, Osman Ugur
dc.contributor.author Yuce, Zeynep
dc.date.accessioned 2025-05-10T17:04:01Z
dc.date.available 2025-05-10T17:04:01Z
dc.date.issued 2020
dc.department T.C. Van Yüzüncü Yıl Üniversitesi en_US
dc.department-temp [Baykal-Kose, Seda; Geyik, Oyku Gonul; Yuce, Zeynep] Dokuz Eylul Univ, Fac Med, Dept Med Biol, Izmir, Turkey; [Acikgoz, Eda] Ege Univ, Fac Med, Dept Histol & Embryol, Izmir, Turkey; [Acikgoz, Eda] Yuzuncu Yil Univ, Fac Med, Dept Histol & Embryol, Van, Turkey; [Yavuz, Ahmet Sinan] Sabanci Univ, Fac Engn & Nat Sci, Dept Mol Biol Genet & Bioengn, Istanbul, Turkey; [Ate, Halil; Ozsan, Guner Hayri] Dokuz Eylul Univ, Fac Med, Dept Hematol, Izmir, Turkey; [Sezerman, Osman Ugur] Acibadem Univ, Sch Med, Dept Biostat & Med Informat, Istanbul, Turkey en_US
dc.description Yuce, Zeynep/0000-0002-2762-0942; Yavuz, Ahmet Sinan/0000-0003-4069-6105; Baykal, Seda/0000-0001-8654-5332; Acikgoz, Eda/0000-0002-6772-3081; Gonul Geyik, Oyku/0000-0003-3014-1253; Sezerman, Osman Ugur/0000-0003-0905-6783 en_US
dc.description.abstract 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 beta-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. en_US
dc.description.sponsorship Dokuz Eylul University Scientific Research Projects [:2012KBSAG092, 2009KBSAG029] en_US
dc.description.sponsorship Dokuz Eylul University Scientific Research Projects, grants no:2012KBSAG092 and 2009KBSAG029. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. en_US
dc.description.woscitationindex Science Citation Index Expanded
dc.identifier.doi 10.1371/journal.pone.0229104
dc.identifier.issn 1932-6203
dc.identifier.issue 2 en_US
dc.identifier.pmid 32106243
dc.identifier.scopus 2-s2.0-85080069625
dc.identifier.scopusquality Q1
dc.identifier.uri https://doi.org/10.1371/journal.pone.0229104
dc.identifier.uri https://hdl.handle.net/20.500.14720/5892
dc.identifier.volume 15 en_US
dc.identifier.wos WOS:000535237000018
dc.identifier.wosquality Q2
dc.language.iso en en_US
dc.publisher Public Library Science en_US
dc.relation.publicationcategory Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı en_US
dc.rights info:eu-repo/semantics/openAccess en_US
dc.title Adaptive Phenotypic Modulations Lead To Therapy Resistance in Chronic Myeloid Leukemia Cells en_US
dc.type Article en_US

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