Evidence map›Paper›PMID 25428260›Full record

ArticleLeukemia2015

KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype.

A Clipson, M Wang, L de Leval, M Ashton-Key, A Wotherspoon, G Vassiliou, N Bolli, C Grove, S Moody, L Escudero-Ibarz and 13 more

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In one paragraph

Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 4 pooled it
7.1field-weighted citation impact, top 2% 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

91 citing papers in PubMed, 4 syntheses or guidelines pooled it, 176 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Pooled it
  4. Pooled it
  5. Article
  6. Article
  7. Decoding IGLL5 Mutation-Mediated BCR Signaling: A Novel Mechanism of CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  20. Complete miRNA-15/16 loss in mice promotes hematopoietic progenitor expansion and a myeloid-biased hyperproliferative state.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article

31 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

23 authors at 8 institutions in 3 countries.

A ClipsonDivision of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK.
M WangDivision of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK.
L de LevalInstitute of Pathology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
M Ashton-KeyDepartment of Cellular Pathology, Southampton University Hospitals National Health Service Trust, Southampton, UK.
A WotherspoonDepartment of Histopathology, Royal Marsden Hospital, London, UK.
G Vassiliou1] Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK [2] Department of Haematology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
N Bolli1] Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK [2] Department of Haematology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
C GroveWellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
S MoodyDivision of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK.
L Escudero-IbarzDivision of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK.
G GundemWellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
K BruggerDepartment of Molecular Genetics, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
X XueDivision of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK.ORCID 0000000278426883
E MiDivision of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK.
A BenchDepartment of Haematology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
M ScottDepartment of Haematology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
H LiuMolecular Malignancy Laboratory, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
G FollowsDepartment of Haematology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
E F RoblesDivision of Oncology, Center for Applied Medical Research CIMA, University of Navarra, Pamplona, Spain.
J A Martinez-ClimentDivision of Oncology, Center for Applied Medical Research CIMA, University of Navarra, Pamplona, Spain.
D OscierDepartment of Haematology, Royal Bournemouth Hospital, Bournemouth, UK.
A J Watkins1] Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK [2] Department of Haematology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
M-Q DuDivision of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK.
Cambridge University Hospitals NHS Foundation Trust · GBUniversity of Cambridge · GBUniversidad de Navarra · ESWellcome Sanger Institute · GBNational Health Service · GBRoyal Bournemouth Hospital · GBRoyal Marsden Hospital · GBUniversity Hospital of Lausanne · CH

Funding

Medical Research CouncilWellcome Trust 095663
6 · The paper itself

Abstract

To characterise the genetics of splenic marginal zone lymphoma (SMZL), we performed whole exome sequencing of 16 cases and identified novel recurrent inactivating mutations in Kruppel-like factor 2 (KLF2), a gene whose deficiency was previously shown to cause splenic marginal zone hyperplasia in mice. KLF2 mutation was found in 40 (42%) of 96 SMZLs, but rarely in other B-cell lymphomas. The majority of KLF2 mutations were frameshift indels or nonsense changes, with missense mutations clustered in the C-terminal zinc finger domains. Functional assays showed that these mutations inactivated the ability of KLF2 to suppress NF-κB activation by TLR, BCR, BAFFR and TNFR signalling. Further extensive investigations revealed common and distinct genetic changes between SMZL with and without KLF2 mutation. IGHV1-2 rearrangement and 7q deletion were primarily seen in SMZL with KLF2 mutation, while MYD88 and TP53 mutations were nearly exclusively found in those without KLF2 mutation. NOTCH2, TRAF3, TNFAIP3 and CARD11 mutations were observed in SMZL both with and without KLF2 mutation. Taken together, KLF2 mutation is the most common genetic change in SMZL and identifies a subset with a distinct genotype characterised by multi-genetic changes. These different genetic changes may deregulate various signalling pathways and generate cooperative oncogenic properties, thereby contributing to lymphomagenesis.

Indexed as

MutationBiopsyCARD Signaling Adaptor ProteinsDNA-Binding ProteinsExomeFrameshift MutationGene Rearrangement, B-Lymphocyte, Heavy ChainGenetic VariationGenotypeGuanylate CyclaseHumansIntracellular Signaling Peptides and ProteinsKruppel-Like Transcription FactorsLymphomaLymphoma, B-Cell, Marginal ZoneMutation, MissenseCARD11 protein, humanCARD Signaling Adaptor ProteinsDNA-Binding ProteinsGuanylate CyclaseIntracellular Signaling Peptides and ProteinsKLF2 protein, humanKruppel-Like Transcription FactorsNOTCH2 protein, humanNuclear ProteinsReceptor, Notch2TNFAIP3 protein, humanTumor Necrosis Factor alpha-Induced Protein 3

Identifiers

PMID25428260
OpenAlexW1982535426

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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.