Targeting UPR signaling pathway by dasatinib as a promising therapeutic approach in chronic myeloid leukemia

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dc.authoridGunduz, Cumhur/0000-0002-6593-3237
dc.authoridAvci, Cigir Biray/0000-0001-8251-4520
dc.authorscopusid56638649300
dc.authorscopusid56638483000
dc.authorscopusid57212299393
dc.authorscopusid57212368912
dc.authorscopusid57212369715
dc.authorscopusid55253674000
dc.authorscopusid57747500300
dc.authorwosidGunduz, Cumhur/GOP-0629-2022
dc.authorwosidBiray Avcı, Cigir/GWV-1665-2022
dc.contributor.authorOzel, Buket
dc.contributor.authorKipcak, Sezgi
dc.contributor.authorBiray Avci, Cigir
dc.contributor.authorSabour Takanlou, Maryam
dc.contributor.authorSabour Takanlou, Leila
dc.contributor.authorTezcanli Kaymaz, Burcin
dc.contributor.authorKaratekin, Ilknur
dc.date.accessioned2023-01-12T19:51:22Z
dc.date.available2023-01-12T19:51:22Z
dc.date.issued2022
dc.departmentN/A/Departmenten_US
dc.description.abstractChronic myeloid leukemia (CML) is a myeloproliferative disease that mediated by BCR/ABL oncogenic signaling. CML can be targeted with the imatinib, dasatinib, and nilotinib TKI inhibitors, the latter two of them have been approved for imatinib-resistant or -intolerant CML patients. The TKIs resistance occurs by different molecular mechanisms, including overexpression of BCR-ABL, mutations in the TKI binding site of BCR/ABL, and ER-stress. Unfolded protein responses (UPR) is a cytoprotective mechanism which is activated by ER-stress. The IRE1, PERK, and ATF6 are three main arms of the UPR mechanism and are activated by a common mechanism involving the dissociation of the ER-chaperone BiP/GP78. There is a correlation between ER-stress, CML progression, and response to TKI treatment. In the present study, we aimed to determine alterations of the expression levels of genes related to UPR pathway signaling after treatment with dasatinib in K562 chronic myeloid leukemia cell line by quantitative RT-PCR relatively. The array-data revealed that treatment with dasatinib significantly decreased the UPR mechanism-related genes (including HSPA1B, HSPA2, HSPA4L, ATF6, ATF6B, CEBPB, PERK, TRIB3, DNAJB, ERN1, and UHRF1) in K562 cells. In conclusion, the results showed that dasatinib regulates the UPR mechanism that plays a significant role in cancer progression and therapy resistance in CML. Thus, dasatinib-induced dysfunction of the UPR mechanism may promise encouraging therapy for CML. [GRAPHICS] .en_US
dc.identifier.doi10.1007/s12032-022-01714-y
dc.identifier.issn1357-0560
dc.identifier.issn1559-131X
dc.identifier.issue9en_US
dc.identifier.pmid35716222en_US
dc.identifier.scopus2-s2.0-85132199358en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1007/s12032-022-01714-y
dc.identifier.urihttps://hdl.handle.net/11454/76263
dc.identifier.volume39en_US
dc.identifier.wosWOS:000812687900005en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherHumana Press Incen_US
dc.relation.ispartofMedical Oncologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subject(ER) stressen_US
dc.subjectUPR mechanismen_US
dc.subjectCMLen_US
dc.subjectBCR-ABLen_US
dc.subjectDasatiniben_US
dc.subjectTKIsen_US
dc.subjectUnfolded Protein Responseen_US
dc.subjectAutocrine Motility Factoren_US
dc.subjectInduced Cell-Deathen_US
dc.subjectBcr-Ablen_US
dc.subjectImatinib-Resistanten_US
dc.subjectStressen_US
dc.subjectEren_US
dc.subjectPhosphorylationen_US
dc.subjectOverexpressionen_US
dc.subjectActivationen_US
dc.titleTargeting UPR signaling pathway by dasatinib as a promising therapeutic approach in chronic myeloid leukemiaen_US
dc.typeArticleen_US

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