Evidence map›Paper›PMID 33503434›Full record

ArticleCell reports2021

Inflammation-driven deaminase deregulation fuels human pre-leukemia stem cell evolution.

Qingfei Jiang, Jane Isquith, Luisa Ladel, Adam Mark, Frida Holm, Cayla Mason, Yudou He, Phoebe Mondala, Isabelle Oliver, Jessica Pham and 20 more

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

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Targeting RNA adenosine editing and modification enzymes for RNA therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
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  15. Article
  16. Article
  17. Stem-Cell Aging and Pathways to Precancer Evolution.The New England journal of medicine · 2023
    Review
  18. 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

30 authors at 4 institutions in 2 countries.

Qingfei JiangDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Jane IsquithDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Luisa LadelDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Adam MarkCenter for Computational Biology & Bioinformatics (CCBB), Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0681, USA.
Frida HolmKarolinska Institutet, Stockholm, Sweden.
Cayla MasonDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Yudou HeDepartment of Cellular and Molecular Medicine and Department of Bioengineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Phoebe MondalaDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Isabelle OliverDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Jessica PhamDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Wenxue MaDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Eduardo ReynosoDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Shawn AliDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Isabella Jamieson MorrisDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Raymond DiepDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Chanond NasamranCenter for Computational Biology & Bioinformatics (CCBB), Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0681, USA.
Guorong XuCenter for Computational Biology & Bioinformatics (CCBB), Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0681, USA.
Roman SasikCenter for Computational Biology & Bioinformatics (CCBB), Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0681, USA.
Sara Brin RosenthalCenter for Computational Biology & Bioinformatics (CCBB), Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0681, USA.
Amanda BirminghamCenter for Computational Biology & Bioinformatics (CCBB), Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0681, USA.
Sanja CosoDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Gabriel PinedaDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Leslie CrewsDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
Mary E DonohoeDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA.
J Craig VenterJ. Craig Venter Institute, La Jolla, CA 92037, USA.
Thomas WhisenantCenter for Computational Biology & Bioinformatics (CCBB), Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0681, USA.
Ruben A MesaMays Cancer Center at UT Health San Antonio MD Anderson, UT Health San Antonio, San Antonio, TX 78229, USA.
Ludmil B AlexandrovDepartment of Cellular and Molecular Medicine and Department of Bioengineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: l2alexandrov@health.ucsd.edu.
Kathleen M FischCenter for Computational Biology & Bioinformatics (CCBB), Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0681, USA. Electronic address: kfisch@health.ucsd.edu.
Catriona JamiesonDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0820, USA. Electronic address: cjamieson@health.ucsd.edu.
University of California San Diego · USJ. Craig Venter Institute · USKarolinska Institutet · SEThe University of Texas Health Science Center at San Antonio · 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
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 P30 CA023100NCI NIH HHS R01 CA205944NIDDK NIH HHS R01 DK114468
6 · The paper itself

Abstract

Inflammation-dependent base deaminases promote therapeutic resistance in many malignancies. However, their roles in human pre-leukemia stem cell (pre-LSC) evolution to acute myeloid leukemia stem cells (LSCs) had not been elucidated. Comparative whole-genome and whole-transcriptome sequencing analyses of FACS-purified pre-LSCs from myeloproliferative neoplasm (MPN) patients reveal APOBEC3C upregulation, an increased C-to-T mutational burden, and hematopoietic stem and progenitor cell (HSPC) proliferation during progression, which can be recapitulated by lentiviral APOBEC3C overexpression. In pre-LSCs, inflammatory splice isoform overexpression coincides with APOBEC3C upregulation and ADAR1p150-induced A-to-I RNA hyper-editing. Pre-LSC evolution to LSCs is marked by STAT3 editing, STAT3β isoform switching, elevated phospho-STAT3, and increased ADAR1p150 expression, which can be prevented by JAK2/STAT3 inhibition with ruxolitinib or fedratinib or lentiviral ADAR1 shRNA knockdown. Conversely, lentiviral ADAR1p150 expression enhances pre-LSC replating and STAT3 splice isoform switching. Thus, pre-LSC evolution to LSCs is fueled by primate-specific APOBEC3C-induced pre-LSC proliferation and ADAR1-mediated splicing deregulation.

Indexed as

Cell ProliferationHumansInflammationLeukemia, Myeloid, AcuteNeoplastic Stem CellsEnter keywords here

Identifiers

PMID33503434
PMCPMC8477897
OpenAlexW3123551255

What OpenQuestion holds

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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.