Evidence map›Paper›PMID 38265938›Full record

ArticleCell reports2024

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, Larisa Balaian, Roman Sasik, Sabina Enlund, Adam Mark, Wenxue Ma and 5 more

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

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
5.8field-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

22 citing papers in PubMed, 25 citations in OpenAlex.

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  19. 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

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 2 countries.

Maria RiveraDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, La Jolla, CA 92037, USA.
Haoran ZhangDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, La Jolla, CA 92037, USA.
Jessica PhamDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Jane IsquithDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Qingchen Jenny ZhouDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, La Jolla, CA 92037, USA.
Larisa BalaianDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Roman SasikCenter for Computational Biology & Bioinformatics (CCBB), University of California, San Diego, La Jolla, CA 92093-0681, USA.
Sabina EnlundDepartment of Women's and Children's Health, Division of Pediatric Oncology and Pediatric Surgery, Karolinska Institutet, Solna, Sweden.
Adam MarkCenter for Computational Biology & Bioinformatics (CCBB), University of California, San Diego, La Jolla, CA 92093-0681, USA.
Wenxue MaDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Frida HolmDepartment of Women's and Children's Health, Division of Pediatric Oncology and Pediatric Surgery, Karolinska Institutet, Solna, Sweden.
Kathleen M FischCenter for Computational Biology & Bioinformatics (CCBB), University of California, San Diego, La Jolla, CA 92093-0681, USA; Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA.
Dennis John KuoMoores Cancer Center, La Jolla, CA 92037, USA; Division of Pediatric Hematology-Oncology, Rady Children's Hospital San Diego, University of California, San Diego, San Diego, CA 92123, USA.
Catriona JamiesonDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, La Jolla, CA 92037, USA.
Qingfei JiangDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, La Jolla, CA 92037, USA. Electronic address: q1jiang@health.ucsd.edu.
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
Elucidate the Role of RNA Editing in Acute T-cell Lymphoblastic Leukemia Initiating CellsR01CA282792 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Qingfei Jiang · 2024 to 2026
$1.4M
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
Profiling Epitranscriptomic RNA editing in Pediatric CancerR03CA287274 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JIANG, QINGFEI · 2024 to 2025
$316k
NCATS NIH HHS UL1 TR001442NCI NIH HHS K22 CA229606NCI NIH HHS R01 CA205944NCI NIH HHS R01 CA282792NCI NIH HHS R03 CA287274
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. 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 editing is a common attribute of relapsed T cell acute lymphoblastic leukemia (T-ALL) regardless of molecular subtype. Consequently, knockdown of ADAR1 severely inhibits LIC self-renewal capacity and prolongs survival in T-ALL patient-derived xenograft models. Mechanistically, ADAR1 directs hyper-editing of immunogenic dsRNA to avoid detection by the innate immune sensor melanoma differentiation-associated protein 5 (MDA5). Moreover, we uncover that the cell-intrinsic level of MDA5 dictates the dependency on the 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 an effective therapeutic strategy for eliminating T-ALL LICs.

Indexed as

Precursor T-Cell Lymphoblastic Leukemia-LymphomaRNA, Double-StrandedAdenosine DeaminaseChronic DiseaseHumansRNA-Binding ProteinsRNA EditingT-LymphocytesADAR protein, humanAdenosine DeaminaseRNA-Binding ProteinsRNA, Double-StrandedCP: CancerCP: Immunologyepitranscriptomeleukemia-initiating cellspediatric leukemiaRNA editing

Identifiers

PMID38265938
PMCPMC10962356
OpenAlexW4391136074

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.