Evidence map›Paper›PMID 35443564›Full record

ArticleHaematologica2022

Persistent DNA damage and oncogenic stress-induced Trem1 promotes leukemia in mice.

Xue Li, Srinivas Chatla, Andrew F Wilson, Limei Wu, Neha Atale, Wei Du

Open access · goldAbstract read
In one paragraph

Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.8field-weighted citation impact, top 32% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. HES1 is required for mouse fetal hematopoiesis.Stem cell research & therapy · 2024
    Article
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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

6 authors at 4 institutions in 2 countries.

Xue LiDivision of Hematology and Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229; Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou.
Srinivas ChatlaFels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140.
Andrew F WilsonCincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
Limei WuDivision of Hematology and Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; UPMC Hillman Cancer Center, Pittsburgh, PA 15213.
Neha AtaleDivision of Hematology and Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; UPMC Hillman Cancer Center, Pittsburgh, PA 15213.
Wei DuDivision of Hematology and Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; UPMC Hillman Cancer Center, Pittsburgh, PA 15213. duw@upmc.edu.
Cincinnati Children's Hospital Medical Center · USUniversity of Pittsburgh · USTemple University · USUPMC Hillman Cancer Center · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
A novel immunometabolism-regulatory axis in inflammatory hematopoiesisR01HL151390 · NHLBI · WEST VIRGINIA UNIVERSITY · PI DU, WEI · 2020 to 2023
$1.5M
NCI NIH HHS P30 CA047904NHLBI NIH HHS R01 HL151390
6 · The paper itself

Abstract

The immune receptor TREM1 (Triggering receptor expressed on myeloid cells 1) is a master regulator of inflammatory response. Compelling evidence suggests important pathological roles for TREM1 in various types of solid tumors. However, the role of TREM1 in hematologic malignancies is not known. Our previous study demonstrated that TREM1 cooperates with diminished DNA damage response to induce expansion of pre-leukemic hematopoietic stem cells (HSC) in mice deficient for the Fanconi anemia gene Fanca. Here we investigated TREM1 in leukemogenesis using mouse models of the DNA repair-deficient Fanca-/- and the oncogenic MLL-AF9 or KrasG12D. We found that Trem1 was highly expressed in preleukemic HSC and leukemia stem cells (LSC). By selective deletion of the Trem1 gene in the hematopoietic compartment, we showed that ablation of Trem1 reduced leukemogenic activity of the pre-leukemic HSC and LSC in mice. Trem1 was required for the proliferation of the pre-leukemic HSC and LSC. Further analysis revealed that Trem1 expression in preleukemic HSC and LSC was associated with persistent DNA damage, prolonged oncogenic stress, and a strong inflammatory signature. Targeting several top Trem1 inflammatory signatures inhibited the proliferation of pre-leukemic HSC and LSC. Collectively, our observations uncover previously unknown expression and function of TREM1 in malignant stem cells, and identify TREM1 as a driver of leukemogenesis.

Indexed as

Fanconi AnemiaLeukemia, Myeloid, AcuteAnimalsCarcinogenesisDNA DamageMiceNeoplastic Stem CellsTriggering Receptor Expressed on Myeloid Cells-1TREM1 protein, mouseTriggering Receptor Expressed on Myeloid Cells-1

Identifiers

PMID35443564
PMCPMC9614537
OpenAlexW4224231988

What OpenQuestion holds

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LicenceCC BY-NC
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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.