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Sender, Sina [VerfasserIn]; Sekora, Anett [VerfasserIn]; Perez, Simon V. [VerfasserIn]; Chabanovska, Oleksandra [VerfasserIn]; Becker, Annegret [VerfasserIn]; Ngezahayo, Anaclet [VerfasserIn]; Junghanss, Christian [VerfasserIn]; Murua Escobar, Hugo [VerfasserIn]

Precursor B-ALL cell lines differentially respond to syk inhibition by entospletinib - [published Version]

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  • Medientyp: E-Artikel; Sonstige Veröffentlichung
  • Titel: Precursor B-ALL cell lines differentially respond to syk inhibition by entospletinib
  • Beteiligte: Sender, Sina [VerfasserIn]; Sekora, Anett [VerfasserIn]; Perez, Simon V. [VerfasserIn]; Chabanovska, Oleksandra [VerfasserIn]; Becker, Annegret [VerfasserIn]; Ngezahayo, Anaclet [VerfasserIn]; Junghanss, Christian [VerfasserIn]; Murua Escobar, Hugo [VerfasserIn]
  • Erschienen: Basel : MDPI, 2021
  • Erschienen in: International Journal of Molecular Sciences 22 (2021), Nr. 2 ; International Journal of Molecular Sciences
  • Ausgabe: published Version
  • Sprache: Englisch
  • DOI: https://doi.org/10.15488/12307; https://doi.org/10.3390/ijms22020592
  • ISSN: 1661-6596
  • Schlagwörter: protein bcl 6 ; RS4 11 cell line ; pyrazine derivative ; human cell ; gene expression regulation ; mitogen activated protein kinase ; metabolism ; Western blotting ; SYK ; B lymphocyte receptor ; B-ALL ; BCR ; apoptosis ; cell proliferation ; controlled study ; protein expression ; Entospletinib ; genetics ; 6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo(1,2-a)pyrazin-8-amine ; antiproliferative activity ; immunofluorescence ; Ento ; indazole derivative ; SU-DHL-4 cell line ; [...]
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  • Beschreibung: Background: Impaired B-cell receptor (BCR) function has been associated with the pro-gress of several B-cell malignancies. The spleen tyrosine kinase (SYK) represents a potential therapeutic target in a subset of B-cell neoplasias. In precursor B-acute lymphoblastic leukemia (B-ALL), the pathogenic role and therapeutic potential of SYK is still controversially discussed. We evaluate the application of the SYK inhibitor entospletinib (Ento) in pre-and pro-B-ALL cell lines, character-izing the biologic and molecular effects. Methods: SYK expression was characterized in pre-B-ALL (NALM-6) and pro-B-ALL cell lines (SEM and RS4;11). The cell lines were exposed to different Ento concentrations and the cell biological response analyzed by proliferation, metabolic activity, apop-tosis induction, cell-cycle distribution and morphology. BCR pathway gene expression and protein modulations were further characterized. Results: Ento significantly induced anti-proliferative and pro-apoptotic effects in NALM-6 and SEM, while barely affecting RS4;11. Targeted RNAseq revealed pronounced gene expression modulation only in NALM-6, while Western Blot analyses demonstrated that vital downstream effector proteins, such as pAKT, pERK, pGSK3β, p53 and BCL-6, were affected by Ento exposure in the inhibitor-sensitive cell lines. Conclusion: Different acting modes of Ento, independent of pre-BCR dependency, were characterized, unexpected in SEM. Ac-cordingly, SYK classifies as a potential target structure in a subset of pro-B-ALLs. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
  • Zugangsstatus: Freier Zugang
  • Rechte-/Nutzungshinweise: Namensnennung (CC BY)