当前位置： SCI文献检索 > NATURE MEDICINE期刊下所有文献 > The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development.

The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development.

Abstract：

:The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center involution and impedes B cell differentiation and class switch recombination. Integrative genomic analyses indicate that KMT2D affects methylation of lysine 4 on histone H3 (H3K4) and expression of a set of genes, including those in the CD40, JAK-STAT, Toll-like receptor and B cell receptor signaling pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3 and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell-activating pathways.

journal_name

Nat Med

journal_title

Nature medicine

authors

Ortega-Molina A,Boss IW,Canela A,Pan H,Jiang Y,Zhao C,Jiang M,Hu D,Agirre X,Niesvizky I,Lee JE,Chen HT,Ennishi D,Scott DW,Mottok A,Hother C,Liu S,Cao XJ,Tam W,Shaknovich R,Garcia BA,Gascoyne RD,Ge K,Shilatif

doi

10.1038/nm.3943

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

1199-208

issue

10

eissn

1078-8956

issn

1546-170X

pii

nm.3943

journal_volume

21

pub_type

杂志文章

相关文献

NATURE MEDICINE文献大全
  • Myeloperoxidase acts as a profibrotic mediator of atrial fibrillation.

    abstract：:Observational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation. However, whether inflammation is the cause or the consequence of atrial fibrillation and which specific inflammatory mediators may increase the atria's susceptibility to fibrillation remain el...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2124

    authors： Rudolph V,Andrié RP,Rudolph TK,Friedrichs K,Klinke A,Hirsch-Hoffmann B,Schwoerer AP,Lau D,Fu X,Klingel K,Sydow K,Didié M,Seniuk A,von Leitner EC,Szoecs K,Schrickel JW,Treede H,Wenzel U,Lewalter T,Nickenig G,Zimmer

    更新日期：2010-04-01 00:00:00

  • An inhibitor of oxidative phosphorylation exploits cancer vulnerability.

    abstract：:Metabolic reprograming is an emerging hallmark of tumor biology and an actively pursued opportunity in discovery of oncology drugs. Extensive efforts have focused on therapeutic targeting of glycolysis, whereas drugging mitochondrial oxidative phosphorylation (OXPHOS) has remained largely unexplored, partly owing to a...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-018-0052-4

    authors： Molina JR,Sun Y,Protopopova M,Gera S,Bandi M,Bristow C,McAfoos T,Morlacchi P,Ackroyd J,Agip AA,Al-Atrash G,Asara J,Bardenhagen J,Carrillo CC,Carroll C,Chang E,Ciurea S,Cross JB,Czako B,Deem A,Daver N,de Groot JF

    更新日期：2018-07-01 00:00:00

  • Bovine beta-lactoglobulin modified by 3-hydroxyphthalic anhydride blocks the CD4 cell receptor for HIV.

    abstract：:Sexual transmission is the most frequent (86%) route of adult HIV-1 transmission worldwide. In the absence of a prophylactic anti-HIV vaccine, other methods of preventing infection should be implemented. Virucidal spermicides have been considered for this purpose, but their application is contraindicated by adverse ef...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0296-230

    authors： Neurath AR,Jiang S,Strick N,Lin K,Li YY,Debnath AK

    更新日期：1996-02-01 00:00:00

  • Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1.

    abstract：:Focal segmental glomerulosclerosis (FSGS) is a frequent and severe glomerular disease characterized by destabilization of podocyte foot processes. We report that transgenic expression of the microRNA miR-193a in mice rapidly induces FSGS with extensive podocyte foot process effacement. Mechanistically, miR-193a inhibi...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3142

    authors： Gebeshuber CA,Kornauth C,Dong L,Sierig R,Seibler J,Reiss M,Tauber S,Bilban M,Wang S,Kain R,Böhmig GA,Moeller MJ,Gröne HJ,Englert C,Martinez J,Kerjaschki D

    更新日期：2013-04-01 00:00:00

  • Functional genomics of Neisseria meningitidis pathogenesis.

    abstract：:The pathogenic bacterium Neisseria meningitidis is an important cause of septicemia and meningitis, especially in childhood. The establishment and maintenance of bacteremic infection is a pre-requisite for all the pathological sequelae of meningococcal infection. To further understand the genetic basis of this essenti...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/81380

    authors： Sun YH,Bakshi S,Chalmers R,Tang CM

    更新日期：2000-11-01 00:00:00

  • A GABAergic system in airway epithelium is essential for mucus overproduction in asthma.

    abstract：:Gamma-aminobutyric acid (GABA) is an important neurotransmitter that, through the subtype A GABA receptor (GABAAR), induces inhibition in the adult brain. Here we show that an excitatory, rather than inhibitory, GABAergic system exists in airway epithelial cells. Both GABAARs and the GABA synthetic enzyme glutamic aci...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1604

    authors： Xiang YY,Wang S,Liu M,Hirota JA,Li J,Ju W,Fan Y,Kelly MM,Ye B,Orser B,O'Byrne PM,Inman MD,Yang X,Lu WY

    更新日期：2007-07-01 00:00:00

  • NOX4-dependent fatty acid oxidation promotes NLRP3 inflammasome activation in macrophages.

    abstract：:Altered metabolism has been implicated in the pathogenesis of inflammatory diseases. NADPH oxidase 4 (NOX4), a source of cellular superoxide anions, has multiple biological functions that may be of importance in inflammation and in the pathogenesis of human metabolic diseases, including diabetes. However, the mechanis...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4153

    authors： Moon JS,Nakahira K,Chung KP,DeNicola GM,Koo MJ,Pabón MA,Rooney KT,Yoon JH,Ryter SW,Stout-Delgado H,Choi AM

    更新日期：2016-09-01 00:00:00

  • Publisher Correction: Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome.

    abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title：Nature medicine

    pub_type： 已发布勘误

    doi：10.1038/s41591-019-0562-8

    authors： Qi X,Yun C,Sun L,Xia J,Wu Q,Wang Y,Wang L,Zhang Y,Liang X,Wang L,Gonzalez FJ,Patterson AD,Liu H,Mu L,Zhou Z,Zhao Y,Li R,Liu P,Zhong C,Pang Y,Jiang C,Qiao J

    更新日期：2019-09-01 00:00:00

  • A20 is an antigen presentation attenuator, and its inhibition overcomes regulatory T cell-mediated suppression.

    abstract：:Regulatory T cells (T(reg) cells) suppress autoreactive immune responses and limit the efficacy of tumor vaccines; however, it remains a challenge to selectively eliminate or inhibit T(reg) cells. In this study, the zinc-finger A20, a negative regulator of the Toll-like receptor and tumor necrosis factor receptor sign...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1721

    authors： Song XT,Evel-Kabler K,Shen L,Rollins L,Huang XF,Chen SY

    更新日期：2008-03-01 00:00:00

  • Restoration of cytomegalovirus-specific CD4+ T-lymphocyte responses after ganciclovir and highly active antiretroviral therapy in individuals infected with HIV-1.

    abstract：:Recent studies of subjects infected with human immunodeficiency virus (HIV-1) have produced conflicting results about the extent of reconstitution possible in the CD4+ lymphocyte repertoire after highly active antiretroviral therapy (HAART). The effect of HAART on the incidence of opportunistic infections will probabl...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0898-953

    authors： Komanduri KV,Viswanathan MN,Wieder ED,Schmidt DK,Bredt BM,Jacobson MA,McCune JM

    更新日期：1998-08-01 00:00:00

  • Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays.

    abstract：:Naturally occurring mutations in HIV-1-infected patients have important implications for therapy and the outcome of clinical studies. However, little is known about the prevalence of mutations that confer resistance to HIV-1 protease inhibitors in isolates derived from patients naive for such inhibitors. In the first ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0796-753

    authors： Kozal MJ,Shah N,Shen N,Yang R,Fucini R,Merigan TC,Richman DD,Morris D,Hubbell E,Chee M,Gingeras TR

    更新日期：1996-07-01 00:00:00

  • Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemia.

    abstract：:T-cell acute lymphoblastic leukemia (T-ALL), unlike other ALL types, is only infrequently associated with chromosomal aberrations, but it was recently shown that most individuals with T-ALL carry activating mutations in the NOTCH1 gene. However, the signaling pathways and target genes responsible for Notch1-induced ne...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1524

    authors： Vilimas T,Mascarenhas J,Palomero T,Mandal M,Buonamici S,Meng F,Thompson B,Spaulding C,Macaroun S,Alegre ML,Kee BL,Ferrando A,Miele L,Aifantis I

    更新日期：2007-01-01 00:00:00

  • IKK-beta links inflammation to obesity-induced insulin resistance.

    abstract：:Inflammation may underlie the metabolic disorders of insulin resistance and type 2 diabetes. IkappaB kinase beta (IKK-beta, encoded by Ikbkb) is a central coordinator of inflammatory responses through activation of NF-kappaB. To understand the role of IKK-beta in insulin resistance, we used mice lacking this enzyme in...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1185

    authors： Arkan MC,Hevener AL,Greten FR,Maeda S,Li ZW,Long JM,Wynshaw-Boris A,Poli G,Olefsky J,Karin M

    更新日期：2005-02-01 00:00:00

  • Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound.

    abstract：:The tumor suppressor p53 inhibits tumor growth primarily through its ability to induce apoptosis. Mutations in p53 occur in at least 50% of human tumors. We hypothesized that reactivation of mutant p53 in such tumors should trigger massive apoptosis and eliminate the tumor cells. To test this, we screened a library of...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0302-282

    authors： Bykov VJ,Issaeva N,Shilov A,Hultcrantz M,Pugacheva E,Chumakov P,Bergman J,Wiman KG,Selivanova G

    更新日期：2002-03-01 00:00:00

  • Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma.

    abstract：:Immune-checkpoint blockade (ICB) has demonstrated efficacy in many tumor types, but predictors of responsiveness to anti-PD1 ICB are incompletely characterized. In this study, we analyzed a clinically annotated cohort of patients with melanoma (n = 144) treated with anti-PD1 ICB, with whole-exome and whole-transcripto...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-019-0654-5

    authors： Liu D,Schilling B,Liu D,Sucker A,Livingstone E,Jerby-Arnon L,Zimmer L,Gutzmer R,Satzger I,Loquai C,Grabbe S,Vokes N,Margolis CA,Conway J,He MX,Elmarakeby H,Dietlein F,Miao D,Tracy A,Gogas H,Goldinger SM,Utikal J

    更新日期：2019-12-01 00:00:00

  • Author Correction: Targeting wild-type KRAS-amplified gastroesophageal cancer through combined MEK and SHP2 inhibition.

    abstract：:In the Supplementary Information originally published with this article, a lane was missing in the β-actin blot in Supplementary Fig. 2. The lane has been added. The error has been corrected in the Supplementary Information associated with this article. ...

    journal_title：Nature medicine

    pub_type： 已发布勘误

    doi：10.1038/s41591-018-0168-6

    authors： Wong GS,Zhou J,Bin Liu J,Wu Z,Xu X,Li T,Xu D,Schumacher SE,Puschhof J,McFarland J,Zou C,Dulak A,Henderson L,Xu P,O'Day E,Rendak R,Liao WL,Cecchi F,Hembrough T,Schwartz S,Szeto C,Rustgi AK,Wong KK,Diehl JA,

    更新日期：2018-10-01 00:00:00

  • Tumor-specific imaging through progression elevated gene-3 promoter-driven gene expression.

    abstract：:Molecular-genetic imaging is advancing from a valuable preclinical tool to a guide for patient management. The strategy involves pairing an imaging reporter gene with a complementary imaging agent in a system that can be used to measure gene expression or protein interaction or track gene-tagged cells in vivo. Tissue-...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2269

    authors： Bhang HE,Gabrielson KL,Laterra J,Fisher PB,Pomper MG

    更新日期：2011-01-01 00:00:00

  • Author Correction: Temporal dynamics in viral shedding and transmissibility of COVID-19.

    abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title：Nature medicine

    pub_type： 已发布勘误

    doi：10.1038/s41591-020-1016-z

    authors： He X,Lau EHY,Wu P,Deng X,Wang J,Hao X,Lau YC,Wong JY,Guan Y,Tan X,Mo X,Chen Y,Liao B,Chen W,Hu F,Zhang Q,Zhong M,Wu Y,Zhao L,Zhang F,Cowling BJ,Li F,Leung GM

    更新日期：2020-09-01 00:00:00

  • Targeted estrogen delivery reverses the metabolic syndrome.

    abstract：:We report the development of a new combinatorial approach that allows for peptide-mediated selective tissue targeting of nuclear hormone pharmacology while eliminating adverse effects in other tissues. Specifically, we report the development of a glucagon-like peptide-1 (GLP-1)-estrogen conjugate that has superior sex...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3009

    authors： Finan B,Yang B,Ottaway N,Stemmer K,Müller TD,Yi CX,Habegger K,Schriever SC,García-Cáceres C,Kabra DG,Hembree J,Holland J,Raver C,Seeley RJ,Hans W,Irmler M,Beckers J,de Angelis MH,Tiano JP,Mauvais-Jarvis F,Perez-Ti

    更新日期：2012-12-01 00:00:00

  • Anti-cancer activity of targeted pro-apoptotic peptides.

    abstract：:We have designed short peptides composed of two functional domains, one a tumor blood vessel 'homing' motif and the other a programmed cell death-inducing sequence, and synthesized them by simple peptide chemistry. The 'homing' domain was designed to guide the peptide to targeted cells and allow its internalization. T...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/12469

    authors： Ellerby HM,Arap W,Ellerby LM,Kain R,Andrusiak R,Rio GD,Krajewski S,Lombardo CR,Rao R,Ruoslahti E,Bredesen DE,Pasqualini R

    更新日期：1999-09-01 00:00:00

  • Vaccines: past, present and future.

    abstract：:The vaccines developed over the first two hundred years since Jenner's lifetime have accomplished striking reductions of infection and disease wherever applied. Pasteur's early approaches to vaccine development, attenuation and inactivation, are even now the two poles of vaccine technology. Today, purification of micr...

    journal_title：Nature medicine

    pub_type： 历史文章,杂志文章

    doi：10.1038/nm1209

    authors： Plotkin SA

    更新日期：2005-04-01 00:00:00

  • Notch3 signaling promotes the development of pulmonary arterial hypertension.

    abstract：:Notch receptor signaling is implicated in controlling smooth muscle cell proliferation and in maintaining smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension is characterized by excessive vascular resistance, smooth muscle cell proliferation in small pulmonary arteries, leading to elevati...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2021

    authors： Li X,Zhang X,Leathers R,Makino A,Huang C,Parsa P,Macias J,Yuan JX,Jamieson SW,Thistlethwaite PA

    更新日期：2009-11-01 00:00:00

  • Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants.

    abstract：:Defects in major histocompatibility complex (MHC) class I-restricted antigen presentation are frequently observed in human cancers and result in escape of tumors from cytotoxic T lymphocyte (CTL) immune surveillance in mice. Here, we show the existence of a unique category of CTLs that can prevent this escape. The CTL...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1381

    authors： van Hall T,Wolpert EZ,van Veelen P,Laban S,van der Veer M,Roseboom M,Bres S,Grufman P,de Ru A,Meiring H,de Jong A,Franken K,Teixeira A,Valentijn R,Drijfhout JW,Koning F,Camps M,Ossendorp F,Kärre K,Ljunggren HG,Mel

    更新日期：2006-04-01 00:00:00

  • Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector.

    abstract：:Hemophilia B is a severe X-linked bleeding diathesis caused by the absence of functional blood coagulation factor IX, and is an excellent candidate for treatment of a genetic disease by gene therapy. Using an adeno-associated viral vector, we demonstrate sustained expression (>17 months) of factor IX in a large-animal...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/4743

    authors： Herzog RW,Yang EY,Couto LB,Hagstrom JN,Elwell D,Fields PA,Burton M,Bellinger DA,Read MS,Brinkhous KM,Podsakoff GM,Nichols TC,Kurtzman GJ,High KA

    更新日期：1999-01-01 00:00:00

  • PAF-mediated pulmonary edema: a new role for acid sphingomyelinase and ceramide.

    abstract：:Platelet-activating factor (PAF) induces pulmonary edema and has a key role in acute lung injury (ALI). Here we show that PAF induces pulmonary edema through two mechanisms: acid sphingomyelinase (ASM)-dependent production of ceramide, and activation of the cyclooxygenase pathway. Agents that interfere with PAF-induce...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm977

    authors： Göggel R,Winoto-Morbach S,Vielhaber G,Imai Y,Lindner K,Brade L,Brade H,Ehlers S,Slutsky AS,Schütze S,Gulbins E,Uhlig S

    更新日期：2004-02-01 00:00:00

  • An immunological epitope selective for pathological monomer-misfolded SOD1 in ALS.

    abstract：:Misfolding of Cu/Zn-superoxide dismutase (SOD1) is emerging as a mechanism underlying motor neuron degeneration in individuals with amyotrophic lateral sclerosis (ALS) who carry a mutant SOD1 gene (SOD1 ALS). Here we describe a structure-guided approach to developing an antibody that specifically recognizes monomer-mi...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1559

    authors： Rakhit R,Robertson J,Vande Velde C,Horne P,Ruth DM,Griffin J,Cleveland DW,Cashman NR,Chakrabartty A

    更新日期：2007-06-01 00:00:00

  • In vivo imaging of glucose uptake and metabolism in tumors.

    abstract：:Tumors have a greater reliance on anaerobic glycolysis for energy production than normal tissues. We developed a noninvasive method for imaging glucose uptake in vivo that is based on magnetic resonance imaging and allows the uptake of unlabeled glucose to be measured through the chemical exchange of protons between h...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3252

    authors： Walker-Samuel S,Ramasawmy R,Torrealdea F,Rega M,Rajkumar V,Johnson SP,Richardson S,Gonçalves M,Parkes HG,Arstad E,Thomas DL,Pedley RB,Lythgoe MF,Golay X

    更新日期：2013-08-01 00:00:00

  • AIDS restriction HLA allotypes target distinct intervals of HIV-1 pathogenesis.

    abstract：:An effective acquired immune response to infectious agents mediated by HLA-restricted T-cell recognition can target different stages of disease pathogenesis. We show here that three distinct HLA alleles known to alter the overall rate of AIDS progression act during distinct intervals after HIV-1 infection. The discret...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1333

    authors： Gao X,Bashirova A,Iversen AK,Phair J,Goedert JJ,Buchbinder S,Hoots K,Vlahov D,Altfeld M,O'Brien SJ,Carrington M

    更新日期：2005-12-01 00:00:00

  • Targeting sphingosine-1-phosphate lyase as an anabolic therapy for bone loss.

    abstract：:Sphingosine-1-phosphate (S1P) signaling influences bone metabolism, but its therapeutic potential in bone disorders has remained unexplored. We show that raising S1P levels in adult mice through conditionally deleting or pharmacologically inhibiting S1P lyase, the sole enzyme responsible for irreversibly degrading S1P...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-018-0005-y

    authors： Weske S,Vaidya M,Reese A,von Wnuck Lipinski K,Keul P,Bayer JK,Fischer JW,Flögel U,Nelsen J,Epple M,Scatena M,Schwedhelm E,Dörr M,Völzke H,Moritz E,Hannemann A,Rauch BH,Gräler MH,Heusch G,Levkau B

    更新日期：2018-05-01 00:00:00

  • Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery.

    abstract：:Here we show that ischemia induces sustained contraction of pericytes on microvessels in the intact mouse brain. Pericytes remain contracted despite successful reopening of the middle cerebral artery after 2 h of ischemia. Pericyte contraction causes capillary constriction and obstructs erythrocyte flow. Suppression o...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2022

    authors： Yemisci M,Gursoy-Ozdemir Y,Vural A,Can A,Topalkara K,Dalkara T

    更新日期：2009-09-01 00:00:00