Evidence map›Paper›PMID 37398458›Full record

ArticleResearch square2023

Malignant A-to-I RNA editing by ADAR1 drives T-cell acute lymphoblastic leukemia relapse via attenuating dsRNA sensing.

Maria Rivera, Haoran Zhang, Jessica Pham, Jane Isquith, Qingchen Jenny Zhou, Roman Sasik, Adam Mark, Wenxue Ma, Frida Holm, Kathleen M Fisch and 3 more

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

Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 3 countries.

Maria RiveraDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Haoran ZhangDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Jessica PhamDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Jane IsquithDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Qingchen Jenny ZhouDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Roman SasikCenter for Computational Biology & Bioinformatics (CCBB), University of California, San Diego, La Jolla, 92093-0681.
Adam MarkCenter for Computational Biology & Bioinformatics (CCBB), University of California, San Diego, La Jolla, 92093-0681.
Wenxue MaDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Frida HolmDepartment of Women's and Children's Health, Division of Pediatric Oncology and Surgery, Karolinska Institutet, Sweden.
Kathleen M FischCenter for Computational Biology & Bioinformatics (CCBB), University of California, San Diego, La Jolla, 92093-0681.
Dennis John KuoMoores Cancer Center, La Jolla, CA 92037, USA.
Catriona JamiesonDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Qingfei JiangDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
University of California San Diego · USKarolinska Institutet · SE

Funding

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
Investigating the role of epitranscriptomic A-to-I RNA editing in T-cell acute lymphoblastic leukemiaK22CA229606 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JIANG, QINGFEI · 2019 to 2021
$574k
NCATS NIH HHS UL1 TR001442NCI NIH HHS K22 CA229606NCI NIH HHS R01 CA205944
6 · The paper itself

Abstract

Leukemia initiating cells (LICs) are regarded as the origin of leukemia relapse and therapeutic resistance. Identifying direct stemness determinants that fuel LIC self-renewal is critical for developing targeted approaches to eliminate LICs and prevent relapse. Here, we show that the RNA editing enzyme ADAR1 is a crucial stemness factor that promotes LIC self-renewal by attenuating aberrant double-stranded RNA (dsRNA) sensing. Elevated adenosine-to-inosine (A-to-I) editing is a common attribute of relapsed T-ALL regardless of molecular subtypes. Consequently, knockdown of ADAR1 severely inhibits LIC self-renewal capacity and prolongs survival in T-ALL PDX models. Mechanistically, ADAR1 directs hyper-editing of immunogenic dsRNA and retains unedited nuclear dsRNA to avoid detection by the innate immune sensor MDA5. Moreover, we uncovered that the cell intrinsic level of MDA5 dictates the dependency on ADAR1-MDA5 axis in T-ALL. Collectively, our results show that ADAR1 functions as a self-renewal factor that limits the sensing of endogenous dsRNA. Thus, targeting ADAR1 presents a safe and effective therapeutic strategy for eliminating T-ALL LICs.

Indexed as

ADAR1RNA editingT-ALL

Identifiers

PMID37398458
PMCPMC10312963
OpenAlexW4380882371

What OpenQuestion holds

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LicenceCC BY
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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.