Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host.

Nature
Marlies MeiselBana Jabri

Abstract

Somatic mutations in tet methylcytosine dioxygenase 2 (TET2), which encodes an epigenetic modifier enzyme, drive the development of haematopoietic malignancies1-7. In both humans and mice, TET2 deficiency leads to increased self-renewal of haematopoietic stem cells with a net developmental bias towards the myeloid lineage1,4,8,9. However, pre-leukaemic myeloproliferation (PMP) occurs in only a fraction of Tet2-/- mice8,9 and humans with TET2 mutations1,3,5-7, suggesting that extrinsic non-cell-autonomous factors are required for disease onset. Here we show that bacterial translocation and increased interleukin-6 production, resulting from dysfunction of the small-intestinal barrier, are critical for the development of PMP in mice that lack Tet2 expression in haematopoietic cells. Furthermore, in symptom-free Tet2-/- mice, PMP can be induced by disrupting intestinal barrier integrity, or in response to systemic bacterial stimuli such as the toll-like receptor 2 agonist. PMP was reversed by antibiotic treatment and failed to develop in germ-free Tet2-/- mice, which illustrates the importance of microbial signals in the development of this condition. Our findings demonstrate the requirement for microbial-dependent inflammation in ...Continue Reading

References

Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Jun 19, 2002·Blood·Scott C KoganUNKNOWN Hematopathology subcommittee of the Mouse Models of Human Cancers Consortium
Aug 24, 2005·British Journal of Haematology·Katerina E PanteliKonstantinos L Bourantas
Apr 25, 2006·Biostatistics·W Evan JohnsonAriel Rabinovic
Feb 5, 2008·Gastroenterology·R Balfour Sartor
May 29, 2009·The New England Journal of Medicine·François DelhommeauOlivier A Bernard
Oct 3, 2009·Haematologica·Olivier KosmiderUNKNOWN Groupe Francophone des Myélodysplasies
Jan 19, 2010·Annual Review of Pathology·Amanda M MarchiandoJerrold R Turner
Oct 13, 2010·Annual Review of Physiology·Le ShenJerrold R Turner
Jun 22, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sigurdur Y KristinssonLynn R Goldin
Aug 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Myunggon KoAnjana Rao
Oct 26, 2011·Microbial Cell Factories·Jerry M Wells
Dec 21, 2013·Methods in Ecology and Evolution·A Murat ErenMitchell L Sogin
Feb 11, 2014·Current Protocols in Immunology·Benoit ChassaingMatam Vijay-Kumar
Aug 27, 2014·Proceedings of the National Academy of Sciences of the United States of America·Andrew T StefkaCathryn R Nagler
Sep 28, 2014·Bioinformatics·Simon AndersWolfgang Huber
Nov 27, 2014·The New England Journal of Medicine·Siddhartha JaiswalBenjamin L Ebert
Nov 27, 2014·The New England Journal of Medicine·Giulio GenoveseSteven A McCarroll
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
Jan 17, 2017·Seminars in Hematology·Max JanSiddhartha Jaiswal
Feb 22, 2017·Trends in Immunology·Steffen Boettcher, Markus G Manz
Feb 6, 2018·Cell Stem Cell·Robert L BowmanRoss L Levine
Feb 7, 2018·Nature Reviews. Clinical Oncology·Daniel E JohnsonJennifer R Grandis

❮ Previous
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Citations

Aug 15, 2018·Blood·Laura BarreyroDaniel T Starczynowski
Jan 12, 2019·Critical Reviews in Food Science and Nutrition·Jun TaoHua-Bin Li
Jan 24, 2019·Blood·Eline Pronk, Marc H G P Raaijmakers
Mar 29, 2019·Nature Reviews. Immunology·Qian Zhang, Xuetao Cao
Jul 16, 2019·Gut Microbes·Rebecca L FineMartin A Kriegel
Nov 2, 2019·Science·Siddhartha Jaiswal, Benjamin L Ebert
Nov 8, 2019·Blood·Margarete A FabreGeorge S Vassiliou
Nov 7, 2019·Annual Review of Pathology·Megan A EvansKenneth Walsh
Jan 23, 2020·International Journal of Molecular Sciences·Christina K FerroneMichael J Rauh
Feb 15, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Susann WinterUwe Platzbecker
Oct 17, 2019·Cold Spring Harbor Perspectives in Medicine·Justin KanerDuane C Hassane
May 1, 2020·Blood·Margarete A Fabre, George S Vassiliou
Sep 16, 2020·EMBO Reports·Shuangqi LiYujiang Geno Shi
May 3, 2019·Nature Communications·Xiaojing YueAnjana Rao
Mar 29, 2020·Science·Caroline J WatsonJamie R Blundell
Mar 17, 2020·Protein & Cell·Danyi LiJun Wang
Oct 1, 2020·Medical Microbiology and Immunology·Xue-Rui YinXiao-Qun Zheng
Feb 28, 2019·Frontiers in Immunology·Chan-Wang J Lio, Anjana Rao
Jun 7, 2020·Nature Genetics·Isaac F López-Moyado, Anjana Rao
Jul 30, 2020·Cancers·Gajalakshmi RamanathanAngela G Fleischman
May 18, 2020·Nature Reviews. Cancer·Masayuki YamashitaEmmanuelle Passegué
Jun 25, 2020·Journal of Pediatric Hematology/oncology·Cameron K TebbiFelicia Migone
Aug 25, 2020·Current Stem Cell Reports·Daniel Hormaechea-AgullaKatherine Y King
Jun 20, 2019·Nature Immunology·Triantafyllos ChavakisGeorge Hajishengallis
Jun 25, 2019·Frontiers in Cell and Developmental Biology·Hong LouStephen K Anderson
Aug 28, 2020·Frontiers in Immunology·Ioannis MitroulisTriantafyllos Chavakis
Oct 8, 2020·Blood Cancer Journal·Michael SchieberJohn D Crispino
Oct 14, 2020·Cancer Science·Hiroyoshi Kunimoto, Hideaki Nakajima
Jan 29, 2020·Cold Spring Harbor Perspectives in Medicine·Oakley C OlsonEmmanuelle Passegué

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Datasets Mentioned

BETA
GSE99333

Methods Mentioned

BETA
flow cytometry
FCS
PCR
scrapings

Software Mentioned

HTSeq
GraphPad Prism
MED
Trim
illumina
ComBAT
R
vegan
TopHat2
R package limma

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