dc.identifier.uri |
http://dx.doi.org/10.15488/12307 |
|
dc.identifier.uri |
https://www.repo.uni-hannover.de/handle/123456789/12405 |
|
dc.contributor.author |
Sender, Sina
|
|
dc.contributor.author |
Sekora, Anett
|
|
dc.contributor.author |
Perez, Simon V.
|
|
dc.contributor.author |
Chabanovska, Oleksandra
|
|
dc.contributor.author |
Becker, Annegret
|
|
dc.contributor.author |
Ngezahayo, Anaclet
|
|
dc.contributor.author |
Junghanss, Christian
|
|
dc.contributor.author |
Murua Escobar, Hugo
|
|
dc.date.accessioned |
2022-06-21T05:47:17Z |
|
dc.date.available |
2022-06-21T05:47:17Z |
|
dc.date.issued |
2021 |
|
dc.identifier.citation |
Sender, S.; Sekora, A.; Perez, S.V.; Chabanovska, O.; Becker, A. et al.: Precursor B-ALL cell lines differentially respond to syk inhibition by entospletinib. In: International Journal of Molecular Sciences 22 (2021), Nr. 2, 592. DOI: https://doi.org/10.3390/ijms22020592 |
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dc.description.abstract |
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. |
eng |
dc.language.iso |
eng |
|
dc.publisher |
Basel : MDPI |
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dc.relation.ispartofseries |
International Journal of Molecular Sciences 22 (2021), Nr. 2 |
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dc.rights |
CC BY 4.0 Unported |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Acute lymphoblastic leukemia |
eng |
dc.subject |
B-ALL |
eng |
dc.subject |
BCR |
eng |
dc.subject |
Ento |
eng |
dc.subject |
Entospletinib |
eng |
dc.subject |
Expression analysis |
eng |
dc.subject |
GS-9973 |
eng |
dc.subject |
Pathway-specific inhibitors |
eng |
dc.subject |
SYK |
eng |
dc.subject |
B lymphocyte receptor |
eng |
dc.subject |
entospletinib |
eng |
dc.subject |
glycogen synthase kinase 3beta |
eng |
dc.subject |
mitogen activated protein kinase |
eng |
dc.subject |
protein bcl 6 |
eng |
dc.subject |
protein kinase B |
eng |
dc.subject |
protein kinase Syk |
eng |
dc.subject |
protein p53 |
eng |
dc.subject |
6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo(1,2-a)pyrazin-8-amine |
eng |
dc.subject |
indazole derivative |
eng |
dc.subject |
protein kinase Syk |
eng |
dc.subject |
pyrazine derivative |
eng |
dc.subject |
SYK protein, human |
eng |
dc.subject |
acute B-cell leukemia cell line |
eng |
dc.subject |
antiproliferative activity |
eng |
dc.subject |
apoptosis |
eng |
dc.subject |
cell cycle |
eng |
dc.subject |
cell metabolism |
eng |
dc.subject |
cell proliferation |
eng |
dc.subject |
controlled study |
eng |
dc.subject |
flow cytometry |
eng |
dc.subject |
gene expression |
eng |
dc.subject |
human |
eng |
dc.subject |
human cell |
eng |
dc.subject |
immunofluorescence |
eng |
dc.subject |
NALM-6 cell line |
eng |
dc.subject |
proapoptotic activity |
eng |
dc.subject |
protein analysis |
eng |
dc.subject |
protein expression |
eng |
dc.subject |
RNA sequencing |
eng |
dc.subject |
RS4 11 cell line |
eng |
dc.subject |
SEM cell line |
eng |
dc.subject |
SU-DHL-4 cell line |
eng |
dc.subject |
SUP-T1 cell line |
eng |
dc.subject |
Western blotting |
eng |
dc.subject |
acute lymphoblastic leukemia |
eng |
dc.subject |
drug effect |
eng |
dc.subject |
gene expression regulation |
eng |
dc.subject |
genetics |
eng |
dc.subject |
metabolism |
eng |
dc.subject |
pathology |
eng |
dc.subject |
pre B lymphocyte |
eng |
dc.subject |
sequence analysis |
eng |
dc.subject |
tumor cell line |
eng |
dc.subject |
Apoptosis |
eng |
dc.subject |
Cell Cycle |
eng |
dc.subject |
Cell Line, Tumor |
eng |
dc.subject |
Cell Proliferation |
eng |
dc.subject |
Flow Cytometry |
eng |
dc.subject |
Gene Expression Regulation, Leukemic |
eng |
dc.subject |
Humans |
eng |
dc.subject |
Indazoles |
eng |
dc.subject |
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma |
eng |
dc.subject |
Precursor Cells, B-Lymphoid |
eng |
dc.subject |
Pyrazines |
eng |
dc.subject |
Sequence Analysis, RNA |
eng |
dc.subject |
Syk Kinase |
eng |
dc.subject.ddc |
570 | Biowissenschaften, Biologie
|
ger |
dc.subject.ddc |
540 | Chemie
|
ger |
dc.title |
Precursor B-ALL cell lines differentially respond to syk inhibition by entospletinib |
|
dc.type |
Article |
|
dc.type |
Text |
|
dc.relation.essn |
1422-0067 |
|
dc.relation.issn |
1661-6596 |
|
dc.relation.doi |
https://doi.org/10.3390/ijms22020592 |
|
dc.bibliographicCitation.issue |
2 |
|
dc.bibliographicCitation.volume |
22 |
|
dc.bibliographicCitation.firstPage |
592 |
|
dc.description.version |
publishedVersion |
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tib.accessRights |
frei zug�nglich |
|