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 |