Evidence map›Paper›PMID 36889320›Full record

ArticleCell reports. Medicine2023

Detection and targeting of splicing deregulation in pediatric acute myeloid leukemia stem cells.

Inge van der Werf, Phoebe K Mondala, S Kathleen Steel, Larisa Balaian, Luisa Ladel, Cayla N Mason, Raymond H Diep, Jessica Pham, Jacqueline Cloos, Gertjan J L Kaspers and 10 more

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

Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
6.7field-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

21 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Spirocyclic β-lactone secondary metabolites modulate spliceosome function.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. MRAS: Master Regulator Analysis of Alternative Splicing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Stem-Cell Aging and Pathways to Precancer Evolution.The New England journal of medicine · 2023
    Review
  19. Article
  20. Article
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

20 authors at 3 institutions in 2 countries.

Inge van der WerfDivision of Regenerative Medicine, Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA; Department of Hematology, Amsterdam University Medical Center, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, the Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Phoebe K MondalaDivision of Regenerative Medicine, Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
S Kathleen SteelDivision of Regenerative Medicine, Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
Larisa BalaianDivision of Regenerative Medicine, Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
Luisa LadelDivision of Regenerative Medicine, Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
Cayla N MasonDivision of Regenerative Medicine, Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
Raymond H DiepDivision of Regenerative Medicine, Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
Jessica PhamDivision of Regenerative Medicine, Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
Jacqueline CloosDepartment of Hematology, Amsterdam University Medical Center, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, the Netherlands.
Gertjan J L KaspersPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Emma Children's Hospital Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Oncology, Amsterdam, the Netherlands.
Warren C ChanDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92037, USA.
Adam MarkCenter for Computational Biology and Bioinformatics (CCBB), University of California, San Diego, La Jolla, CA 92037, USA.
James J La ClairDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92037, USA.
Peggy WentworthDivision of Regenerative Medicine, Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
Kathleen M FischCenter for Computational Biology and Bioinformatics (CCBB), University of California, San Diego, La Jolla, CA 92037, USA.
Leslie A CrewsDivision of Regenerative Medicine, Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
Thomas C WhisenantCenter for Computational Biology and Bioinformatics (CCBB), University of California, San Diego, La Jolla, CA 92037, USA.
Michael D BurkartDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92037, USA.
Mary E DonohoeDivision of Regenerative Medicine, Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
Catriona H M JamiesonDivision of Regenerative Medicine, Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: cjamieson@health.ucsd.edu.
University of California San Diego · USCancer Center Amsterdam · NLEmma Kinderziekenhuis · NL

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
Characterization of the Role of ADAR1 in Oncogenic Transformation of ProgenitorsR01CA205944 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JAMIESON, CATRIONA HELEN MACLEOD · 2017 to 2021
$1.8M
Defining the Niche-dependent Role of RNA Editing in Aged and MDS Hematopoietic Stem and Progenitor Cell DysfunctionR01DK114468 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JAMIESON, CATRIONA HELEN MACLEOD · 2017 to 2021
$1.7M
NCATS NIH HHS UL1 TR001442NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA205944NIDDK NIH HHS R01 DK114468
6 · The paper itself

Abstract

Pediatric acute myeloid leukemia (pAML) is typified by high relapse rates and a relative paucity of somatic DNA mutations. Although seminal studies show that splicing factor mutations and mis-splicing fuel therapy-resistant leukemia stem cell (LSC) generation in adults, splicing deregulation has not been extensively studied in pAML. Herein, we describe single-cell proteogenomics analyses, transcriptome-wide analyses of FACS-purified hematopoietic stem and progenitor cells followed by differential splicing analyses, dual-fluorescence lentiviral splicing reporter assays, and the potential of a selective splicing modulator, Rebecsinib, in pAML. Using these methods, we discover transcriptomic splicing deregulation typified by differential exon usage. In addition, we discover downregulation of splicing regulator RBFOX2 and CD47 splice isoform upregulation. Importantly, splicing deregulation in pAML induces a therapeutic vulnerability to Rebecsinib in survival, self-renewal, and lentiviral splicing reporter assays. Taken together, the detection and targeting of splicing deregulation represent a potentially clinically tractable strategy for pAML therapy.

Indexed as

Leukemia, Myeloid, AcuteStem CellsAdultChildHumansMutationProtein IsoformsRepressor ProteinsRNA SplicingRNA Splicing FactorsProtein IsoformsRBFOX2 protein, humanRepressor ProteinsRNA Splicing FactorsCD47embryonic stem cellshematopoietic stem cellspediatric AMLpre-mRNA splicingRBFOX2SF3B1splicing modulation

Identifiers

PMID36889320
PMCPMC10040387
OpenAlexW4323354428

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.