Evidence map›Paper›PMID 25676421›Full record

ArticleLeukemia2015

Early B-cell-specific inactivation of ATM synergizes with ectopic CyclinD1 expression to promote pre-germinal center B-cell lymphomas in mice.

K Yamamoto, B J Lee, C Li, R L Dubois, E Hobeika, G Bhagat, S Zha

Open access · bronzeAbstract read
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 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

11 citing papers in PubMed, 20 citations in OpenAlex.

  1. Trial
  2. Review
  3. Mechanisms of the role of proto-oncogene activation in promoting malignant transformation of mature B cells.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024
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  4. Review
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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

7 authors at 3 institutions in 2 countries.

K Yamamoto1] Institute for Cancer Genetics, College for Physicians and Surgeons, Columbia University, New York, NY, USA [2] Graduate Program for Pathobiology and Molecular Medicine, College for Physicians and Surgeons, Columbia University, New York, NY, USA.
B J LeeInstitute for Cancer Genetics, College for Physicians and Surgeons, Columbia University, New York, NY, USA.
C LiInstitute for Cancer Genetics, College for Physicians and Surgeons, Columbia University, New York, NY, USA.
R L DuboisInstitute for Cancer Genetics, College for Physicians and Surgeons, Columbia University, New York, NY, USA.
E Hobeika1] Centre for Biological Signaling Studies BIOSS, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany [2] Department of Molecular Immunology, Albert-Ludwigs-Universität Freiburg and Max Planck Institute for Immunobiology, Freiburg, Germany.
G BhagatDepartment of Pathology and Cell Biology, College for Physicians and Surgeons, Columbia University, New York, NY, USA.ORCID 000000016250048X
S Zha1] Institute for Cancer Genetics, College for Physicians and Surgeons, Columbia University, New York, NY, USA [2] Department of Pathology and Cell Biology, College for Physicians and Surgeons, Columbia University, New York, NY, USA [3] Department of Pediatrics, College for Physicians and Surgeons, Columbia University, New York, NY, USA.
Cancer Genetics (United States) · USColumbia University · USUniversity of Freiburg · DE

Funding

The Role of CTIP in Lymphocyte Development and LymphomagenesisP01CA174653 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI RABADAN, RAUL · 2014 to 2024
$17.6M
The role of ATM in the suppression of lymphoid malignancyR01CA158073 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Shan Zha · 2011 to 2026
$5.7M
DNA-PKCS Phosphorylation in DNA Repair and Chromosomal TranslocationsR01CA184187 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ZHA, SHAN · 2015 to 2019
$1.8M
NCI NIH HHS 1R01CA158073NCI NIH HHS P01 CA174653NCI NIH HHS R01 CA158073NCI NIH HHS R01 CA184187
6 · The paper itself

Abstract

Ataxia telangiectasia-mutated (ATM) kinase is a master regulator of the DNA damage response. ATM is frequently inactivated in human B-cell non-Hodgkin lymphomas, including ~50% of mantle cell lymphomas (MCLs) characterized by ectopic expression of CyclinD1. Here we report that early and robust deletion of ATM in precursor/progenitor B cells causes cell autonomous, clonal mature B-cell lymphomas of both pre- and post-germinal center (GC) origins. Unexpectedly, naive B-cell-specific deletion of ATM is not sufficient to induce lymphomas in mice, highlighting the important tumor suppressor function of ATM in immature B cells. Although EμCyclinD1 is not sufficient to induce lymphomas, EμCyclinD1 accelerates the kinetics and increases the incidence of clonal lymphomas in ATM-deficient B-cells and skews the lymphomas toward pre-GC-derived small lymphocytic neoplasms, sharing morphological features of human MCL. This is in part due to CyclinD1-driven expansion of ATM-deficient naive B cells with genomic instability, which promotes the deletions of additional tumor suppressor genes (i.e. Trp53, Mll2, Rb1 and Cdkn2a). Together these findings define a synergistic function of ATM and CyclinD1 in pre-GC B-cell proliferation and lymphomagenesis and provide a prototypic animal model to study the pathogenesis of human MCL.

Indexed as

AnimalsAtaxia Telangiectasia Mutated ProteinsBlotting, SouthernBlotting, WesternB-LymphocytesCell ProliferationCyclin D1Flow CytometryGenomic InstabilityGerminal CenterHumansImmunoenzyme TechniquesIn Situ Hybridization, FluorescenceLymphoma, B-CellLymphopeniaMiceAtaxia Telangiectasia Mutated ProteinsCyclin D1

Identifiers

PMID25676421
PMCPMC5282516
OpenAlexW2018410771

What OpenQuestion holds

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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.