Media type: Text; E-Article Title: Precursor B-ALL cell lines differentially respond to syk inhibition by entospletinib Contributor: Sender, Sina [Author]; Sekora, Anett [Author]; Perez, Simon V. [Author]; Chabanovska, Oleksandra [Author]; Becker, Annegret [Author]; Ngezahayo, Anaclet [Author]; Junghanss, Christian [Author]; Murua Escobar, Hugo [Author] imprint: Basel : MDPI, 2021 Published in: International Journal of Molecular Sciences 22 (2021), Nr. 2 ; International Journal of Molecular Sciences Issue: published Version Language: English DOI: https://doi.org/10.15488/12307; https://doi.org/10.3390/ijms22020592 ISSN: 1661-6596 Keywords: acute B-cell leukemia cell line ; controlled study ; SEM cell line ; SU-DHL-4 cell line ; human ; protein kinase B ; protein p53 ; apoptosis ; immunofluorescence ; RS4 11 cell line ; cell metabolism ; NALM-6 cell line ; metabolism ; protein analysis ; SYK ; Ento ; antiproliferative activity ; Entospletinib ; protein bcl 6 ; mitogen activated protein kinase ; Acute lymphoblastic leukemia ; cell cycle ; gene expression ; drug effect ; [...] Origination: Footnote: Diese Datenquelle enthält auch Bestandsnachweise, die nicht zu einem Volltext führen. Description: 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. Access State: Open Access Rights information: Attribution (CC BY)