Evidence map›Paper›PMID 36803553›Full record

ArticleCell stem cell2023

Reversal of malignant ADAR1 splice isoform switching with Rebecsinib.

Leslie A Crews, Wenxue Ma, Luisa Ladel, Jessica Pham, Larisa Balaian, S Kathleen Steel, Phoebe K Mondala, Raymond H Diep, Christina N Wu, Cayla N Mason and 10 more

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

Article in Cell stem cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
9.4field-weighted citation impact, top 1% 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

46 citing papers in PubMed, 61 citations in OpenAlex.

  1. Review
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  14. Deaminase Modulation Driving a New Era in Drug Development.International journal of molecular sciences · 2025
    Review
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  17. Article
  18. Targeting RNA adenosine editing and modification enzymes for RNA therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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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

20 authors at 2 institutions in 1 country.

Leslie A CrewsDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Wenxue MaDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA.
Luisa LadelDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA.
Jessica PhamDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA.
Larisa BalaianDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
S Kathleen SteelDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA.
Phoebe K MondalaDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA.
Raymond H DiepDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA.
Christina N WuDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA.
Cayla N MasonDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA.
Inge van der WerfDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA.
Isabelle OliverDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA.
Eduardo ReynosoDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA.
Gabriel PinedaDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA.
Thomas C WhisenantCenter for Computational Biology & Bioinformatics (CCBB), Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Peggy WentworthDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA.
James J La ClairDepartments of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Qingfei JiangDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA.
Michael D BurkartDepartments of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Catriona H M JamiesonDepartment of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, University of California, San Diego, La Jolla, CA 92037, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: cjamieson@health.ucsd.edu.
Sanford Consortium for Regenerative Medicine · USUniversity of California, San Diego · US

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

Adenosine deaminase acting on RNA1 (ADAR1) preserves genomic integrity by preventing retroviral integration and retrotransposition during stress responses. However, inflammatory-microenvironment-induced ADAR1p110 to p150 splice isoform switching drives cancer stem cell (CSC) generation and therapeutic resistance in 20 malignancies. Previously, predicting and preventing ADAR1p150-mediated malignant RNA editing represented a significant challenge. Thus, we developed lentiviral ADAR1 and splicing reporters for non-invasive detection of splicing-mediated ADAR1 adenosine-to-inosine (A-to-I) RNA editing activation; a quantitative ADAR1p150 intracellular flow cytometric assay; a selective small-molecule inhibitor of splicing-mediated ADAR1 activation, Rebecsinib, which inhibits leukemia stem cell (LSC) self-renewal and prolongs humanized LSC mouse model survival at doses that spare normal hematopoietic stem and progenitor cells (HSPCs); and pre-IND studies showing favorable Rebecsinib toxicokinetic and pharmacodynamic (TK/PD) properties. Together, these results lay the foundation for developing Rebecsinib as a clinical ADAR1p150 antagonist aimed at obviating malignant microenvironment-driven LSC generation.

Indexed as

Adenosine DeaminaseHematopoietic Stem CellsAnimalsMiceProtein IsoformsADAR1 protein, mouseAdenosine DeaminaseProtein IsoformsADAR1cancer stem cellscancer therapyhematopoiesisleukemia stem cellsmyelofibrosismyeloproliferative neoplasmsRNA editingsecondary AMLsplicing

Identifiers

PMID36803553
PMCPMC10134781
OpenAlexW4321116319

What OpenQuestion holds

Textmetadata
LicenceTDM
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.