Evidence map›Paper›PMID 32204435›Full record

ArticleCancers2020

Glucocorticoid Resistant Pediatric Acute Lymphoblastic Leukemia Samples Display Altered Splicing Profile and Vulnerability to Spliceosome Modulation.

Rocco Sciarrillo, Anna Wojtuszkiewicz, Irsan E Kooi, Leticia G Leon, Edwin Sonneveld, Roland P Kuiper, Gerrit Jansen, Elisa Giovannetti, Gertjan J L Kaspers, Jacqueline Cloos

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

13 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
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  5. Review
  6. Research progress and therapeutic prospect of PHF5A acting as a new target for malignant tumors.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022
    Review
  7. Alternative RNA splicing defects in pediatric cancers: new insights in tumorigenesis and potential therapeutic vulnerabilities.Annals of oncology : official journal of the European Society for Medical Oncology · 2022
    Review
  8. Article
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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

10 authors at 4 institutions in 2 countries.

Rocco SciarrilloAmsterdam UMC, Vrije Universiteit Amsterdam, Departments of Pediatric Oncology, Hematology and Medical Oncology, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands.
Anna WojtuszkiewiczAmsterdam UMC, Vrije Universiteit Amsterdam, Departments of Pediatric Oncology and Hematology, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands.
Irsan E KooiAmsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Department of Clinical Genetics, 1081 HV Amsterdam, The Netherlands.
Leticia G LeonErasmus MC, University Medical Center Rotterdam, Department of Immunology, 3000 CA Rotterdam, The Netherlands.
Edwin SonneveldPrincess Máxima Center for Pediatric Oncology, 3584 CX Utrecht, The Netherlands.ORCID 0000-0002-1869-0957
Roland P KuiperPrincess Máxima Center for Pediatric Oncology, 3584 CX Utrecht, The Netherlands.ORCID 0000-0003-4928-3809
Gerrit JansenAmsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Immunology and Rheumatology Center, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands.
Elisa GiovannettiAmsterdam UMC, Vrije Universiteit Amsterdam, Department of Medical Oncology, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands.ORCID 0000-0002-7565-7504
Gertjan J L KaspersPrincess Máxima Center for Pediatric Oncology, 3584 CX Utrecht, The Netherlands.
Jacqueline CloosAmsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands.
Amsterdam University Medical Centers · NLPrincess Máxima Center · NLErasmus MC · NLFondazione Pisa · IT

Funding

Cancer Center Amsterdam Foundation 2013Cancer Center Amsterdam Foundation 2015Stichting Kinderen Kankervrij 151
6 · The paper itself

Abstract

Glucocorticoid (GC) resistance is a crucial determinant of inferior response to chemotherapy in pediatric acute lymphoblastic leukemia (ALL); however, molecular mechanisms underlying this phenomenon are poorly understood. Deregulated splicing is a common feature of many cancers, which impacts drug response and constitutes an attractive therapeutic target. Therefore, the aim of the current study was to characterize global splicing profiles associated with GC resistance and determine whether splicing modulation could serve as a novel therapeutic option for GC-resistant patients. To this end, 38 primary ALL samples were profiled using RNA-seq-based differential splicing analysis. The impact of splicing modulators was investigated in GC-resistant leukemia cell lines and primary leukemic specimens. Our findings revealed, for the first time, markedly distinct splicing landscapes in ALL samples of B-cell precursor (BCP)-ALL and T-ALL lineages. Differential splicing events associated with GC resistance were involved in RNA processing, a direct response to GCs, survival signaling, apoptosis, cell cycle regulation and energy metabolism. Furthermore, our analyses showed that GC-resistant ALL cell lines and primary samples are sensitive to splicing modulation, alone and in combination with GC. Together, these findings suggest that aberrant splicing is associated with GC resistance and splicing modulators deserve further interest as a novel treatment option for GC-resistant patients.

Indexed as

alternative splicingglucocorticoid resistancepediatric acute lymphoblastic leukemiaRNA sequencingSF3B modulators

Identifiers

PMID32204435
PMCPMC7140081
OpenAlexW3012450271

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.