Evidence map›Paper›PMID 26728187›Full record

ArticleNature communications2016

The KDM3A-KLF2-IRF4 axis maintains myeloma cell survival.

Hiroto Ohguchi, Teru Hideshima, Manoj K Bhasin, Gullu T Gorgun, Loredana Santo, Michele Cea, Mehmet K Samur, Naoya Mimura, Rikio Suzuki, Yu-Tzu Tai and 8 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 1 pooled it
9.8field-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

79 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.

  1. Pooled it
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  11. The Direction of Modern Therapies in Waldenström Macroglobulinaemia.Journal of cellular and molecular medicine · 2025
    Review
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19 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

18 authors at 7 institutions in 3 countries.

Hiroto OhguchiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Teru HideshimaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Manoj K BhasinBIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
Gullu T GorgunDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Loredana SantoMGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Michele CeaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.ORCID http://orcid.org/0000-0003-3345-0799
Mehmet K SamurDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Naoya MimuraDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Rikio SuzukiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Yu-Tzu TaiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Ruben D CarrascoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Noopur RajeMGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Paul G RichardsonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Nikhil C MunshiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Hideo HarigaeDepartment of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan.
Takaomi SandaCancer Science Institute of Singapore, Department of Medicine, National University of Singapore, Singapore 117599, Singapore.ORCID http://orcid.org/0000-0003-1621-4954
Juro SakaiDivision of Metabolic Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan.
Kenneth C AndersonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Dana-Farber Cancer Institute · USMassachusetts General Hospital · USBeth Israel Deaconess Medical Center · USNational University of Singapore · SGRoxbury Community College · USThe University of Tokyo · JPTohoku University · JP

Funding

Trageting the Multiple Myeloma EpigenomeP50CA100707 · NCI · DANA-FARBER CANCER INSTITUTE · PI ANDERSON, KENNETH C., MUNSHI, NIKHIL C. · 2003 to 2023
$45.0M
Targeting Genomic Instability and Evolution in MyelomaP01CA155258 · NCI · DANA-FARBER CANCER INST · PI Jill Corre · 2011 to 2026
$32.5M
Targeting Myeloma Cell-Host Bone Marrow InteractionsP01CA078378 · NCI · DANA-FARBER CANCER INSTITUTE · PI RITZ, JEROME · 1998 to 2014
$26.2M
MUC1-C Oncoprotein Evades Immune Destruction in Non-small Cell Lung CancerR01CA166480 · NCI · DANA-FARBER CANCER INST · PI KUFE, DONALD W., WONG, KWOK KIN · 2012 to 2021
$6.3M
Role of Cytokines in Myeloma PathogenesisR01CA050947 · NCI · DANA-FARBER CANCER INSTITUTE · PI ANDERSON, KENNETH C., MITSIADES, CONSTANTINE S. · 1991 to 2018
$5.1M
Functional and biologic significance of deacetylase3 inhibition in myelomaR01CA178264 · NCI · DANA-FARBER CANCER INST · PI ANDERSON, KENNETH C., HIDESHIMA, TERU · 2014 to 2018
$1.8M
NCI NIH HHS P01 CA078378NCI NIH HHS P01 CA155258NCI NIH HHS P50 CA100707NCI NIH HHS R01 CA050947NCI NIH HHS R01 CA166480NCI NIH HHS R01 CA178264PHS HHS P0-1 155258PHS HHS P0-1 78378PHS HHS R0-1 50947PHS HHS SPORE P50 100707
6 · The paper itself

Abstract

KDM3A is implicated in tumorigenesis; however, its biological role in multiple myeloma (MM) has not been elucidated. Here we identify KDM3A-KLF2-IRF4 axis dependence in MM. Knockdown of KDM3A is toxic to MM cells in vitro and in vivo. KDM3A maintains expression of KLF2 and IRF4 through H3K9 demethylation, and knockdown of KLF2 triggers apoptosis. Moreover, KLF2 directly activates IRF4 and IRF4 reciprocally upregulates KLF2, forming a positive autoregulatory circuit. The interaction of MM cells with bone marrow milieu mediates survival of MM cells. Importantly, silencing of KDM3A, KLF2 or IRF4 both decreases MM cell adhesion to bone marrow stromal cells and reduces MM cell homing to the bone marrow, in association with decreased ITGB7 expression in MAF-translocated MM cell lines. Our results indicate that the KDM3A-KLF2-IRF4 pathway plays an essential role in MM cell survival and homing to the bone marrow, and therefore represents a therapeutic target.

Indexed as

Cell AdhesionCell Line, TumorCell MovementGene Expression Regulation, NeoplasticGene Knockdown TechniquesHistonesHumansInterferon Regulatory Factor-4Interferon Regulatory FactorsJumonji Domain-Containing Histone DemethylasesKruppel-Like Transcription FactorsMultiple MyelomaHistonesInterferon Regulatory Factor-4Interferon Regulatory FactorsJumonji Domain-Containing Histone DemethylasesKDM3A protein, humanKLF2 protein, humanKruppel-Like Transcription Factors

Identifiers

PMID26728187
PMCPMC4728406
OpenAlexW2254742941

What OpenQuestion holds

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LicenceCC BY
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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.