Evidence map›Paper›PMID 33435587›Full record

ArticleInternational journal of molecular sciences2021

Precursor B-ALL Cell Lines Differentially Respond to SYK Inhibition by Entospletinib.

Sina Sender, Anett Sekora, Simon Villa Perez, Oleksandra Chabanovska, Annegret Becker, Anaclet Ngezahayo, Christian Junghanss, Hugo Murua Escobar

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 7 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Sina SenderDivision of Medicine, Department of Hematology, Oncology and Palliative Medicine, University of Rostock, 18057 Rostock, Germany.ORCID 0000-0001-5816-9296
Anett SekoraDivision of Medicine, Department of Hematology, Oncology and Palliative Medicine, University of Rostock, 18057 Rostock, Germany.
Simon Villa PerezDivision of Medicine, Department of Hematology, Oncology and Palliative Medicine, University of Rostock, 18057 Rostock, Germany.
Oleksandra ChabanovskaDivision of Medicine, Department of Hematology, Oncology and Palliative Medicine, University of Rostock, 18057 Rostock, Germany.
Annegret BeckerDepartment of Cell Physiology and Biophysics, Institute of Cell Biology and Biophysics, Leibniz University Hannover, 30419 Hannover, Germany.
Anaclet NgezahayoDepartment of Cell Physiology and Biophysics, Institute of Cell Biology and Biophysics, Leibniz University Hannover, 30419 Hannover, Germany.ORCID 0000-0002-3686-923X
Christian JunghanssDivision of Medicine, Department of Hematology, Oncology and Palliative Medicine, University of Rostock, 18057 Rostock, Germany.
Hugo Murua EscobarDivision of Medicine, Department of Hematology, Oncology and Palliative Medicine, University of Rostock, 18057 Rostock, Germany.
University of Rostock · DELeibniz University Hannover · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImpaired B-cell receptor (BCR) function has been associated with the progress 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, characterizing the biologic and molecular effects.

methodsSYK 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, apoptosis induction, cell-cycle distribution and morphology. BCR pathway gene expression and protein modulations were further characterized.

resultsEnto 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.

conclusionDifferent acting modes of Ento, independent of pre-BCR dependency, were characterized, unexpected in SEM. Accordingly, SYK classifies as a potential target structure in a subset of pro-B-ALLs.

Indexed as

ApoptosisCell CycleCell Line, TumorCell ProliferationFlow CytometryGene Expression Regulation, LeukemicHumansIndazolesMorpholinesPrecursor B-Cell Lymphoblastic Leukemia-LymphomaPrecursor Cells, B-LymphoidPyrazinesSequence Analysis, RNASyk Kinase6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo(1,2-a)pyrazin-8-amineIndazolesMorpholinesPyrazinesSyk KinaseSYK protein, humanacute lymphoblastic leukemiaB-ALLBCREntoentospletinibexpression analysisGS-9973pathway-specific inhibitorsSYK

Identifiers

PMID33435587
PMCPMC7827334
OpenAlexW3120034182

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.