Evidence map›Paper›PMID 25862704›Full record

ArticleHaematologica2015

Targeting the spliceosome in chronic lymphocytic leukemia with the macrolides FD-895 and pladienolide-B.

Manoj K Kashyap, Deepak Kumar, Reymundo Villa, James J La Clair, Chris Benner, Roman Sasik, Harrison Jones, Emanuela M Ghia, Laura Z Rassenti, Thomas J Kipps and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Haematologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
6.4field-weighted citation impact, top 3% 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

54 citing papers in PubMed, 82 citations in OpenAlex.

  1. RNA splicing in health and disease.Molecular biomedicine · 2026
    Review
  2. Article
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  8. Article
  9. Article
  10. Life science alliance · 2023
    Article
  11. Article
  12. Role of RNA Splicing in Regulation of Cancer Stem Cell.Current stem cell research & therapy · 2023
    Article
  13. Cancers · 2022
    Review
  14. RNA splicing: a dual-edged sword for hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2022
    Review
  15. Review
  16. Article
  17. Review
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  20. Review
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

12 authors at 2 institutions in 1 country.

Manoj K KashyapMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Deepak KumarMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Reymundo VillaDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
James J La ClairDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Chris BennerIntegrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, La Jolla, CA, USA.
Roman SasikCenter for Computational Biology, Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
Harrison JonesMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Emanuela M GhiaMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Laura Z RassentiMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA CLL Research Consortium, and Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Thomas J KippsMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA CLL Research Consortium, and Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Michael D BurkartDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Januario E CastroMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA CLL Research Consortium, and Department of Medicine, University of California, San Diego, La Jolla, CA, USA jecastro@ucsd.edu mburkart@ucsd.edu.
University of California San Diego · USSalk Institute for Biological Studies · US

Funding

Tissue CoreP01CA081534 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KIPPS, THOMAS J · 2000 to 2016
$59.5M
Site Specific Protein Labeling In Vivo Through Genetically Engineered PhosphopantR01GM086225 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BURKART, MICHAEL D. · 2008 to 2011
$2.4M
NCI NIH HHS P01 CA081534NCI NIH HHS P01-CA081534NIGMS NIH HHS R01 GM086225NIGMS NIH HHS R01-GM086225
6 · The paper itself

Abstract

RNA splicing plays a fundamental role in human biology. Its relevance in cancer is rapidly emerging as demonstrated by spliceosome mutations that determine the prognosis of patients with hematologic malignancies. We report studies using FD-895 and pladienolide-B in primary leukemia cells derived from patients with chronic lymphocytic leukemia and leukemia-lymphoma cell lines. We found that FD-895 and pladienolide-B induce an early pattern of mRNA intron retention - spliceosome modulation. This process was associated with apoptosis preferentially in cancer cells as compared to normal lymphocytes. The pro-apoptotic activity of these compounds was observed regardless of poor prognostic factors such as Del(17p), TP53 or SF3B1 mutations and was able to overcome the protective effect of culture conditions that resemble the tumor microenvironment. In addition, the activity of these compounds was observed not only in vitro but also in vivo using the A20 lymphoma murine model. Overall, these findings give evidence for the first time that spliceosome modulation is a valid target in chronic lymphocytic leukemia and provide an additional rationale for the development of spliceosome modulators for cancer therapy.

Indexed as

AnimalsAnti-Bacterial AgentsAntineoplastic AgentsApoptosisCell Line, TumorEpoxy CompoundsGene ExpressionHumansLeukemia, Lymphocytic, Chronic, B-CellMacrolidesMiceMice, Inbred BALB CMutationPhosphoproteinsRibonucleoprotein, U2 Small NuclearRNA, MessengerAnti-Bacterial AgentsAntineoplastic AgentsEpoxy CompoundsFD 895MacrolidesPhosphoproteinspladienolide BRibonucleoprotein, U2 Small NuclearRNA, MessengerRNA Splicing FactorsSF3B1 protein, humanTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID25862704
PMCPMC4486229
OpenAlexW2028599797

What OpenQuestion holds

Textmetadata
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.