Evidence map›Paper›PMID 31253791›Full record

ArticleNature communications2019

Mutant H3 histones drive human pre-leukemic hematopoietic stem cell expansion and promote leukemic aggressiveness.

Meaghan Boileau, Margret Shirinian, Tenzin Gayden, Ashot S Harutyunyan, Carol C L Chen, Leonie G Mikael, Heather M Duncan, Andrea L Neumann, Patricia Arreba-Tutusaus, Nicolas De Jay and 16 more

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

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

31 citing papers in PubMed, 47 citations in OpenAlex.

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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

26 authors at 6 institutions in 2 countries.

Meaghan BoileauDivision of Experimental Medicine, McGill University and McGill University Heath Centre Research Institute, Montreal, H4A 3J1, QC, Canada.
Margret ShirinianDepartment of Experimental Pathology, Immunology, and Microbiology, American University of Beirut, Beirut, 1107 2020, Lebanon.
Tenzin GaydenDepartment of Human Genetics, McGill University, Montreal, H3A 1B1, QC, Canada.ORCID http://orcid.org/0000-0003-0138-8038
Ashot S HarutyunyanDepartment of Human Genetics, McGill University, Montreal, H3A 1B1, QC, Canada.ORCID http://orcid.org/0000-0002-9050-9315
Carol C L ChenDepartment of Human Genetics, McGill University, Montreal, H3A 1B1, QC, Canada.
Leonie G MikaelDepartment of Pediatrics, McGill University and McGill University Heath Centre Research Institute, Montreal, H4A 3J1, QC, Canada.
Heather M DuncanDivision of Experimental Medicine, McGill University and McGill University Heath Centre Research Institute, Montreal, H4A 3J1, QC, Canada.ORCID http://orcid.org/0000-0001-6176-4846
Andrea L NeumannResearch Institute of the McGill University Health Centre and McGill University, Montreal, H4A 3J1, QC, Canada.
Patricia Arreba-TutusausResearch Institute of the McGill University Health Centre and McGill University, Montreal, H4A 3J1, QC, Canada.
Nicolas De JayDepartment of Human Genetics, McGill University, Montreal, H3A 1B1, QC, Canada.
Michele ZeiniehDepartment of Human Genetics, McGill University, Montreal, H3A 1B1, QC, Canada.
Katya RossokhataDepartment of Human Genetics, McGill University, Montreal, H3A 1B1, QC, Canada.ORCID http://orcid.org/0000-0002-5715-5957
Yelu ZhangResearch Institute of the McGill University Health Centre and McGill University, Montreal, H4A 3J1, QC, Canada.
Hamid NikbakhtDepartment of Human Genetics, McGill University, Montreal, H3A 1B1, QC, Canada.ORCID http://orcid.org/0000-0003-0209-5667
Carine MouawadDepartment of Experimental Pathology, Immunology, and Microbiology, American University of Beirut, Beirut, 1107 2020, Lebanon.
Radwan MassoudDepartment of Internal Medicine, American University of Beirut, Beirut, 1107 2020, Lebanon.ORCID http://orcid.org/0000-0001-9275-3840
Felice FreyDepartment of Experimental Pathology, Immunology, and Microbiology, American University of Beirut, Beirut, 1107 2020, Lebanon.
Rihab NasrDepartment of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, 1107 2020, Lebanon.
Jean El CheikhDepartment of Internal Medicine, American University of Beirut, Beirut, 1107 2020, Lebanon.ORCID http://orcid.org/0000-0003-2846-9428
Marwan El SabbanDepartment of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, 1107 2020, Lebanon.
Claudia L KleinmanDepartment of Human Genetics, McGill University, Montreal, H3A 1B1, QC, Canada.
Rami MahfouzDepartment of Pathology and Laboratory Medicine, American University of Beirut, Beirut, 1107 2020, Lebanon.
Mark D MindenPrincess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, M5G 2C1, ON, Canada.
Nada JabadoDepartment of Human Genetics, McGill University, Montreal, H3A 1B1, QC, Canada.ORCID http://orcid.org/0000-0003-2485-3692
Ali BazarbachiDepartment of Internal Medicine, American University of Beirut, Beirut, 1107 2020, Lebanon.
Kolja EppertDepartment of Pediatrics, McGill University and McGill University Heath Centre Research Institute, Montreal, H4A 3J1, QC, Canada. kolja.eppert@mcgill.ca.ORCID http://orcid.org/0000-0001-9061-8856
American University of Beirut · LBMcGill University Health Centre · CAMcGill University · CAJewish General Hospital · CAMcGill University and Génome Québec Innovation Centre · CAUniversity Health Network · CA

Funding

Shared Resources Core 2: Quantitative Proteomics CoreP01CA196539 · NCI · ROCKEFELLER UNIVERSITY · PI MUIR, TOM · 2015 to 2024
$17.6M
Comprehensive Sequencing and Analysis of Variation in NHLBI CohortsUC2HL102925 · NHLBI · BROAD INSTITUTE, INC. · PI ALTSHULER, DAVID, GABRIEL, STACEY · 2010 to 2010
$14.7M
Northwest Genomics CenterUC2HL102926 · NHLBI · UNIVERSITY OF WASHINGTON · PI GREEN, PHILIP P, NICKERSON, DEBORAH A · 2010 to 2010
$14.0M
Northwest Genomics CenterRC2HL102926 · NHLBI · UNIVERSITY OF WASHINGTON · PI GREEN, PHILIP P, NICKERSON, DEBORAH A · 2009 to 2009
$11.0M
Comprehensive Sequencing and Analysis of Variation in NHLBI CohortsRC2HL102925 · NHLBI · BROAD INSTITUTE, INC. · PI ALTSHULER, DAVID, GABRIEL, STACEY · 2009 to 2009
$10.2M
ARRA - NHLBI Lung Cohorts Sequencing ProjectRC2HL102923 · NHLBI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, BARNES, KATHLEEN C · 2009 to 2009
$2.6M
ARRA - NHLBI Lung Cohorts Sequencing ProjectUC2HL102923 · NHLBI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, BARNES, KATHLEEN C · 2010 to 2010
$2.6M
WHI Sequencing Project (WHISP)UC2HL102924 · NHLBI · OHIO STATE UNIVERSITY · PI CARLSON, CHRISTOPHER S, JACKSON, REBECCA D · 2010 to 2010
$2.4M
WHI Sequencing Project (WHISP)RC2HL102924 · NHLBI · OHIO STATE UNIVERSITY · PI CARLSON, CHRISTOPHER S, JACKSON, REBECCA D · 2009 to 2009
$2.1M
Human Exome Sequencing in Six Well-Phenotyped NHLBI CohortsUC2HL103010 · NHLBI · UNIVERSITY OF VIRGINIA · PI RICH, STEPHEN S. · 2010 to 2010
$1.5M
Human Exome Sequencing in Six Well-Phenotyped NHLBI CohortsRC2HL103010 · NHLBI · UNIVERSITY OF VIRGINIA · PI RICH, STEPHEN S. · 2009 to 2009
$817k
NCI NIH HHS P01 CA196539NHLBI NIH HHS RC2 HL102923NHLBI NIH HHS RC2 HL102924NHLBI NIH HHS RC2 HL102925NHLBI NIH HHS RC2 HL102926NHLBI NIH HHS RC2 HL103010NHLBI NIH HHS UC2 HL102923NHLBI NIH HHS UC2 HL102924NHLBI NIH HHS UC2 HL102925NHLBI NIH HHS UC2 HL102926NHLBI NIH HHS UC2 HL103010
6 · The paper itself

Abstract

Our ability to manage acute myeloid leukemia (AML) is limited by our incomplete understanding of the epigenetic disruption central to leukemogenesis, including improper histone methylation. Here we examine 16 histone H3 genes in 434 primary AML samples and identify Q69H, A26P, R2Q, R8H and K27M/I mutations (1.6%), with higher incidence in secondary AML (9%). These mutations occur in pre-leukemic hematopoietic stem cells (HSCs) and exist in the major leukemic clones in patients. They increase the frequency of functional HSCs, alter differentiation, and amplify leukemic aggressiveness. These effects are dependent on the specific mutation. H3K27 mutation increases the expression of genes involved in erythrocyte and myeloid differentiation with altered H3K27 tri-methylation and K27 acetylation. The functional impact of histone mutations is independent of RUNX1 mutation, although they at times co-occur. This study establishes that H3 mutations are drivers of human pre-cancerous stem cell expansion and important early events in leukemogenesis.

Indexed as

EpigenomicsAnimalsAnimals, Genetically ModifiedAntineoplastic AgentsBase SequenceBone Marrow CellsCell DifferentiationCell Transformation, NeoplasticDNADrosophila melanogasterGene Expression Regulation, LeukemicHematopoiesisHematopoietic Stem CellsHistonesHumansLeukemia, Myeloid, AcuteAntineoplastic AgentsDNAHistones

Identifiers

PMID31253791
PMCPMC6599207
OpenAlexW2954634447

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.