Evidence map›Paper›PMID 40749668›Full record

ArticleStem cell reports2025

Impaired DNA damage responses and inflammatory signaling underpin hematopoietic stem cell defects in Gata2 haploinsufficiency.

Ali Abdelfattah, Ahmad Habib, Leigh-Anne Thomas, Juan Bautista Menendez-Gonzalez, Alhomidi Almotiri, Hind Alqahtani, Hannah Lawson, Sarab Taha, Millie Steadman, Radhika Athalye and 9 more

Abstract read
In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. GATA2 deficiency exacerbates chronic liver injuryWorld journal of stem cells · 2026
    Article
  2. 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

19 authors.

Ali AbdelfattahDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, Zarqa, Jordan; European Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff, UK.
Ahmad HabibEuropean Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff, UK.
Leigh-Anne ThomasEuropean Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff, UK.
Juan Bautista Menendez-GonzalezEuropean Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff, UK.
Alhomidi AlmotiriDepartment of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Shaqra University, Shaqra, Saudi Arabia; Cardiff University, School of Biosciences, Cardiff, UK.
Hind AlqahtaniEuropean Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff, UK.
Hannah LawsonInstitute of Cancer Research, University of London, London, UK.
Sarab TahaEuropean Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff, UK.
Millie SteadmanEuropean Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff, UK.
Radhika AthalyeEuropean Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff, UK.
Alex GibbsEuropean Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff, UK.
Hamed AlzahraniEuropean Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff, UK.
Ali AlshahraniEuropean Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff, UK.
Alice CatoEuropean Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff, UK.
Peter GilesWales Gene Park and Wales Cancer Research Centre, Division of Cancer and Genetics, Cardiff University, School of Medicine, Cardiff, UK.
Alex TonksDepartment of Hematology, Division of Cancer and Genetics, Cardiff University, School of Medicine, Cardiff, UK.
Ashleigh S BoydDepartment of Surgical Biotechnology, Division of Surgery and Interventional Science, Royal Free Hospital, University College London, London, UK; Institute of Immunity and Transplantation, University College London, London, UK.
Kamil R KrancInstitute of Cancer Research, University of London, London, UK.
Neil P RodriguesEuropean Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff, UK. Electronic address: rodriguesn@cardiff.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Clinical GATA2 haploinsufficiency results in immunodeficiency that evolves to leukemia. How GATA2 haploinsufficiency disrupts the functionality of hematopoietic stem/progenitor cells (HSCs/HSPCs) to facilitate pre-leukemia development is poorly defined. Using a hematopoietic-specific conditional mouse model of Gata2 haploinsufficiency, we identified pervasive defects in HSPC differentiation in young adult Gata2 haploinsufficient mice and perturbed HSC self-renewal following transplantation. These alterations aligned with deregulated global DNA damage responses and inflammatory cell signaling from Gata2 haploinsufficient HSCs. We also discovered genetic interplay between Gata2 and Asxl1, a secondary mutation leading to leukemia in GATA2 deficiency syndromes. HSCs from young adult compound Gata2/Asxl1 haploinsufficient mice were hyperproliferative, functionally compromised after transplantation, and displayed a broad pre-leukemia transcriptomic program. Thus, Gata2 haploinsufficiency triggers HSC genomic instability. Our data further suggest that secondary mutations like ASXL1 exploit this impaired HSC genomic integrity to nurture a pre-leukemic state in GATA2 haploinsufficiency syndromes.

Indexed as

DNA DamageGATA2 Transcription FactorHaploinsufficiencyHematopoietic Stem CellsInflammationSignal TransductionAnimalsCell DifferentiationGenomic InstabilityMiceRepressor ProteinsAsxl1 protein, mouseGata2 protein, mouseGATA2 Transcription FactorRepressor ProteinsDNA damage responseGATA2 haploinsufficiencyhematopoietic stem cellsinflammationpre-leukemia

Identifiers

PMID40749668
PMCPMC12365849

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.