Evidence map›Paper›PMID 27377587›Full record

Trial reportThe Journal of experimental medicine2016

Genetically distinct leukemic stem cells in human CD34- acute myeloid leukemia are arrested at a hemopoietic precursor-like stage.

Lynn Quek, Georg W Otto, Catherine Garnett, Ludovic Lhermitte, Dimitris Karamitros, Bilyana Stoilova, I-Jun Lau, Jessica Doondeea, Batchimeg Usukhbayar, Alison Kennedy and 23 more

Open access · bronzeAbstract readClinical TrialMulticenter Study
In one paragraph

Trial report in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 1 pooled it
13.4field-weighted citation impact, top 1% 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

94 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.

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34 more citing papers are in PubMed but not listed here.

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

33 authors at 5 institutions in 1 country.

Lynn QuekMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK Department of Hematology, Oxford University Hospital National Health Service Trust, Oxford OX3 9DU, England, UK.
Georg W OttoMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK.ORCID 0000-0002-3929-948X
Catherine GarnettMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK.
Ludovic LhermitteMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK.ORCID 0000-0003-2498-0376
Dimitris KaramitrosMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK.
Bilyana StoilovaMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK.
I-Jun LauMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK Department of Hematology, Oxford University Hospital National Health Service Trust, Oxford OX3 9DU, England, UK.ORCID 0000-0003-1727-3243
Jessica DoondeeaMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK.
Batchimeg UsukhbayarMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK.ORCID 0000-0001-5914-3848
Alison KennedyMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK.
Marlen MetznerMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK.
Nicolas GoardonMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK.ORCID 0000-0002-5093-0922
Adam IveyDepartment of Genetics, King's College London, London WC2R 2LS, England, UK.
Christopher AllenCancer Institute, University College London, London WC1E 6BT, England, UK.ORCID 0000-0002-5310-0529
Rosemary GaleCancer Institute, University College London, London WC1E 6BT, England, UK.ORCID 0000-0002-0103-1787
Benjamin DaviesNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University Hospital National Health Service Trust, Oxford OX3 9DU, England, UK.ORCID 0000-0002-4878-0697
Alexander SternbergDepartment of Hematology, Great Western Hospital National Health Service Foundation Trust, Swindon SN3 6BB, England, UK.
Sally KillickDepartment of Hematology, Royal Bournemouth and Christchurch Hospital National Health Service Trust, Bournemouth BH7 7DW, England, UK.ORCID 0000-0002-7769-1562
Hannah HunterDepartment of Hematology, Plymouth Hospitals National Health Service Trust, Plymouth PL6 8DH, England, UK.
Paul CahalinDepartment of Hematology, Blackpool, Fylde and Wyre Hospitals National Health Service Trust, Blackpool FY3 8NR, England, UK.ORCID 0000-0001-7358-2396
Andrew PriceNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University Hospital National Health Service Trust, Oxford OX3 9DU, England, UK.
Andrew CarrNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University Hospital National Health Service Trust, Oxford OX3 9DU, England, UK.ORCID 0000-0001-5940-1464
Mike GriffithsWest Midlands Regional Genetics Laboratory, Birmingham B15 2TG, England, UK.ORCID 0000-0001-5112-2882
Paul VirgoDepartment of Immunology, North Bristol National Health Service Trust, Bristol BS10 5NB, England, UK.
Stephen MackinnonCancer Institute, University College London, London WC1E 6BT, England, UK Department of Hematology, University College London Hospital National Health Service Foundation Trust, London NW1 2BU, England, UK.ORCID 0000-0002-6289-4295
David GrimwadeDepartment of Genetics, King's College London, London WC2R 2LS, England, UK.
Sylvie FreemanSchool of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, England, UK Department of Haematology, University Hospitals Birmingham National Health Service Foundation Trust, Birmingham B15 2TH, England, UK.
Nigel RussellCentre for Clinical Hematology, Nottingham University Hospitals National Health Service Trust, Nottingham NG5 1PB, England, UK.
Charles CraddockDepartment of Clinical Haematology, University of Birmingham, Birmingham B15 2TT, England, UK Department of Clinical Haematology, University Hospitals Birmingham National Health Service Foundation Trust, Birmingham B15 2TH, England, UK.ORCID 0000-0001-5041-6678
Adam MeadMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK Department of Hematology, Oxford University Hospital National Health Service Trust, Oxford OX3 9DU, England, UK.
Andrew PeniketDepartment of Hematology, Oxford University Hospital National Health Service Trust, Oxford OX3 9DU, England, UK.ORCID 0000-0002-6833-9882
Catherine PorcherMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK.ORCID 0000-0002-9015-5203
Paresh VyasMedical Research Council, Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 2JD, England, UK Department of Hematology, Oxford University Hospital National Health Service Trust, Oxford OX3 9DU, England, UK paresh.vyas@imm.ox.ac.uk.ORCID 0000-0003-3931-0914
National Health Service · GBUniversity of Oxford · GBKing's College London · GBUniversity College London · GBWessex Regional Genetics Laboratory · GB

Funding

Cancer Research UK C7893/A12796Department of Health RP-PG-0108-10093Medical Research Council G1000729Medical Research Council MC_UU_12009/11Medical Research Council MC_UU_12009/16Medical Research Council MC_UU_12009/9Medical Research Council MR/L006340/1Medical Research Council MR/M00919X/1Wellcome Trust
6 · The paper itself

Abstract

Our understanding of the perturbation of normal cellular differentiation hierarchies to create tumor-propagating stem cell populations is incomplete. In human acute myeloid leukemia (AML), current models suggest transformation creates leukemic stem cell (LSC) populations arrested at a progenitor-like stage expressing cell surface CD34. We show that in ∼25% of AML, with a distinct genetic mutation pattern where >98% of cells are CD34(-), there are multiple, nonhierarchically arranged CD34(+) and CD34(-) LSC populations. Within CD34(-) and CD34(+) LSC-containing populations, LSC frequencies are similar; there are shared clonal structures and near-identical transcriptional signatures. CD34(-) LSCs have disordered global transcription profiles, but these profiles are enriched for transcriptional signatures of normal CD34(-) mature granulocyte-macrophage precursors, downstream of progenitors. But unlike mature precursors, LSCs express multiple normal stem cell transcriptional regulators previously implicated in LSC function. This suggests a new refined model of the relationship between LSCs and normal hemopoiesis in which the nature of genetic/epigenetic changes determines the disordered transcriptional program, resulting in LSC differentiation arrest at stages that are most like either progenitor or precursor stages of hemopoiesis.

Indexed as

Leukemia, Myeloid, AcuteAnimalsAntigens, CD34Granulocyte-Macrophage Progenitor CellsHeterograftsHumansMaleMiceMice, Inbred NODMice, SCIDNeoplasm ProteinsNeoplasm TransplantationNeoplastic Stem CellsAntigens, CD34Neoplasm Proteins

Identifiers

PMID27377587
PMCPMC4986529
OpenAlexW2471542144

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.