High TUBB2A expression in childhood T-ALL is correlated with the clinical outcome

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dc.authoridyildirmak, zeynep yildiz/0000-0003-3939-2761|NG, YUK YIN/0000-0001-9755-6045|Ozdemir, Gul Nihal/0000-0002-3204-4353|ERBILGIN, YÜCEL/0000-0001-6969-6649
dc.authorwosidNg, Ozden Hatirnaz/W-8018-2018
dc.authorwosidSayitoglu, Muge/B-6578-2015
dc.authorwosidyildirmak, zeynep yildiz/AEG-9521-2022
dc.authorwosidNG, YUK YIN/AAG-7977-2020
dc.authorwosidOzdemir, Gul Nihal/L-9600-2013
dc.authorwosidOzdemir, Gul Nihal/AAO-9962-2020
dc.authorwosidERBILGIN, YÜCEL/AAC-4769-2020
dc.contributor.authorKhodzhaev, Khusan
dc.contributor.authorNg, Ozden Hatirnaz
dc.contributor.authorTugcu, Deniz
dc.contributor.authorErbilgin, Yucel
dc.contributor.authorNg, Yuk Yin
dc.contributor.authorCelkan, Tiraje
dc.contributor.authorTimur, Cetin
dc.date.accessioned2024-07-18T20:47:31Z
dc.date.available2024-07-18T20:47:31Z
dc.date.issued2020
dc.departmentİstanbul Bilgi Üniversitesien_US
dc.description.abstractIntroduction Microtubules are polymers that perform functions such as mitosis, intracellular transport, cell morphology, and ciliary and flagellar motility. Since microtubules are taking active part in cell division, they are among direct targets of several antimitotic drugs. Methods Expression levels of tubulin isotypes were analyzed in microarray data of childhood diagnostic T-ALL samples (n = 31) and healthy thymocytes (n = 7). Findings were validated with qPCR in separate T-ALL cohort (n = 48), and clinical correlation analyses were performed.TUBB2A's effects were tested with siRNA-mediated knockdown in MOLT4 cell line, and apoptosis assay was carried out at 24, 48, and 72 hours time points. Results In microarray data,TUBB2Awas found to be the only differentially expressed tubulin isotype (adj.Pvalue = .01), which was validated by qPCR (P = .02). Samples representing differentiation stages of T cell showed an increasing trend ofTUBB2Atoward mature T-cell stage.TUBB2Aexpression was significantly higher in high-risk group patients (P = .026) and in a group with WBC counts >100 (x10(9)cells/L) (P = .029). HighTUBB2Awas also found to be a predictor of shorter OS (P = .029) and RFS (P = .042). Conclusion Aberrant expression of TUBB isotypes can affect the balance of microtubules or microtubule-associated proteins, which might lead to drug resistance/relapse. Contribution of cytoskeleton proteins to drug resistance needs further investigation, and understanding aberrant expression and mode of action of microtubules will improve therapy strategies.en_US
dc.description.sponsorshipIstanbul University [TYL-2016-21490]; Istanbul Development Agency [TR10/15/YNK/0093]en_US
dc.description.sponsorshipThis study was funded by Istanbul University with the project number TYL-2016-21490 and Istanbul Development Agency (TR10/15/YNK/0093).en_US
dc.identifier.doi10.1111/ijlh.13235
dc.identifier.endpage588en_US
dc.identifier.issn1751-5521
dc.identifier.issn1751-553X
dc.identifier.issue5en_US
dc.identifier.scopus2-s2.0-85086332566en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage581en_US
dc.identifier.urihttps://doi.org/10.1111/ijlh.13235
dc.identifier.urihttps://hdl.handle.net/11411/7827
dc.identifier.volume42en_US
dc.identifier.wosWOS:000539858400001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofInternational Journal of Laboratory Hematologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectLeukemiaen_US
dc.subjectMicroarrayen_US
dc.subjectT-Allen_US
dc.subjectTubb2aen_US
dc.subjectTubulinen_US
dc.subjectAcute Lymphoblastic-Leukemiaen_US
dc.subjectIii Beta-Tubulinen_US
dc.subjectGene-Expressionen_US
dc.subjectChemotherapyen_US
dc.subjectResistanceen_US
dc.subjectIsotypesen_US
dc.subjectCanceren_US
dc.subjectImpacten_US
dc.subjectChemosensitivityen_US
dc.subjectDifferentiationen_US
dc.titleHigh TUBB2A expression in childhood T-ALL is correlated with the clinical outcome
dc.typeArticle

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