Evidence map›Paper›PMID 32330454›Full record

ArticleCancer cell2020

C/EBPα and GATA-2 Mutations Induce Bilineage Acute Erythroid Leukemia through Transformation of a Neomorphic Neutrophil-Erythroid Progenitor.

Cristina Di Genua, Simona Valletta, Mario Buono, Bilyana Stoilova, Connor Sweeney, Alba Rodriguez-Meira, Amit Grover, Roy Drissen, Yiran Meng, Ryan Beveridge and 7 more

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

Article in Cancer cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.1field-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

18 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
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  5. Article
  6. Acute Erythroid Leukemia: From Molecular Biology to Clinical Outcomes.International journal of molecular sciences · 2024
    Review
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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

17 authors at 5 institutions in 2 countries.

Cristina Di GenuaMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
Simona VallettaMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
Mario BuonoMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
Bilyana StoilovaMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK; NIHR Oxford Biomedical Research Center, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.
Connor SweeneyMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK; NIHR Oxford Biomedical Research Center, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.
Alba Rodriguez-MeiraMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
Amit GroverMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
Roy DrissenMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
Yiran MengMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
Ryan BeveridgeMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
Zahra AboukhalilMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK; NIHR Oxford Biomedical Research Center, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.
Dimitris KaramitrosMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK; NIHR Oxford Biomedical Research Center, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.
Mirjam E BelderbosPrincess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, the Netherlands.
Leonid BystrykhEuropean Research Institute for the Biology of Ageing, University Medical Center Groningen, 9713 AV Groningen, the Netherlands.
Supat ThongjueaMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK; MRC WIMM Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; NIHR Oxford Biomedical Research Center, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.
Paresh VyasMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK; NIHR Oxford Biomedical Research Center, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.
Claus NerlovMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK. Electronic address: claus.nerlov@imm.ox.ac.uk.
MRC Weatherall Institute of Molecular Medicine · GBUniversity of Oxford · GBJohn Radcliffe Hospital · GBPrincess Máxima Center · NLUniversity Medical Center Groningen · NL

Funding

Medical Research Council G0900892Medical Research Council G0902418Medical Research Council G1000729Medical Research Council MC_U137961146Medical Research Council MC_UU_00016/11Medical Research Council MC_UU_00016/7Medical Research Council MC_UU_12009Medical Research Council MC_UU_12009/11Medical Research Council MC_UU_12009/7Medical Research Council MC_UU_12025Medical Research Council MR/L008963/1Medical Research Council MR/M00919X/1Medical Research Council MR/T015055/1
6 · The paper itself

Abstract

Acute erythroid leukemia (AEL) commonly involves both myeloid and erythroid lineage transformation. However, the mutations that cause AEL and the cell(s) that sustain the bilineage leukemia phenotype remain unknown. We here show that combined biallelic Cebpa and Gata2 zinc finger-1 (ZnF1) mutations cooperatively induce bilineage AEL, and that the major leukemia-initiating cell (LIC) population has a neutrophil-monocyte progenitor (NMP) phenotype. In pre-leukemic NMPs Cebpa and Gata2 mutations synergize by increasing erythroid transcription factor (TF) expression and erythroid TF chromatin access, respectively, thereby installing ectopic erythroid potential. This erythroid-permissive chromatin conformation is retained in bilineage LICs. These results demonstrate that synergistic transcriptional and epigenetic reprogramming by leukemia-initiating mutations can generate neomorphic pre-leukemic progenitors, defining the lineage identity of the resulting leukemia.

Indexed as

Cell LineageMutationAgedAllelesAnimalsCCAAT-Enhancer-Binding Protein-alphaCell DifferentiationCell Transformation, NeoplasticDisease Models, AnimalErythroid Precursor CellsFemaleGATA1 Transcription FactorGATA2 Transcription FactorHumansLeukemia, Erythroblastic, AcuteMaleCCAAT-Enhancer-Binding Protein-alphaGATA1 protein, humanGATA1 Transcription FactorGATA2 protein, humanGATA2 Transcription Factoracute erythroid leukemiaacute myeloid leukemiaCEBPAchromatin accessibilityGATA2leukemia-initiating celllineage primingoncogene co-operation

Identifiers

PMID32330454
PMCPMC7218711
OpenAlexW3014469486

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.