Evidence map›Paper›PMID 25512612›Full record

ArticleMolecular and cellular biology2015

A zebrafish model of myelodysplastic syndrome produced through tet2 genomic editing.

Evisa Gjini, Marc R Mansour, Jeffry D Sander, Nadine Moritz, Ashley T Nguyen, Michiel Kesarsing, Emma Gans, Shuning He, Si Chen, Myunggon Ko and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

36 citing papers in PubMed, 63 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Learning from Zebrafish Hematopoiesis.Advances in experimental medicine and biology · 2023
    Review
  5. Depletion ofFrontiers in hematology · 2023
    Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Summary of animal models of myelodysplastic syndrome.Animal models and experimental medicine · 2021
    Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Modeling hematopoietic disorders in zebrafish.Disease models & mechanisms · 2019
    Review
  18. Disruption ofDisease models & mechanisms · 2019
    Article
  19. Article
  20. Review
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 6 institutions in 3 countries.

Evisa GjiniDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
Marc R MansourDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA Department of Hematology, UCL Cancer Institute, University College London, London, United Kingdom.
Jeffry D SanderMolecular Pathology Unit, Center for Computational and Integrative Biology, and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
Nadine MoritzDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
Ashley T NguyenDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
Michiel KesarsingDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
Emma GansDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
Shuning HeDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
Si ChenDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
Myunggon KoDivision of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
You-Yi KuangHeilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences No. 232, Daoli District Harbin, Heilongjiang, People's Republic of China.
Song YangDivision of Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Yi ZhouDivision of Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Scott RodigBrigham and Women's Hospital, Boston, Massachusetts, USA.
Leonard I ZonDivision of Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
J Keith JoungMolecular Pathology Unit, Center for Computational and Integrative Biology, and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
Anjana RaoDivision of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
A Thomas LookDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA thomas_look@dfci.harvard.edu.
Dana-Farber Cancer Institute · USHarvard University · USLa Jolla Institute for Immunology · USBrigham and Women's Hospital · USCenter for Cancer Research · USChinese Academy of Fishery Sciences · CN

Funding

MOLECULAR IMMUNOLOGY AND TUMOR BIOLOGYT32CA009216 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Michael Langenau · 1985 to 2026
$10.6M
Cancer Biology in the ZebrafishR01CA103846 · NCI · CHILDREN'S HOSPITAL BOSTON · PI ZON, LEONARD IRA · 2003 to 2022
$7.5M
EMBRYONIC HEMATOPOIESISR01HL048801 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI ZON, LEONARD IRA · 1992 to 2016
$5.7M
ADVANCING ZINC FINGER NUCLEASES FOR TARGETED GENOME MANIPULATIONR01GM088040 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH, PETERSON, RANDALL T · 2009 to 2016
$4.5M
Advancing stem cell technologies using engineered zinc finger proteinsDP1GM105378 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH · 2012 to 2014
$2.6M
Genetic Basis of Myeloid Neoplasia--Mutagenesis ScreensR01CA093152 · NCI · DANA-FARBER CANCER INSTITUTE · PI LOOK, A THOMAS · 2001 to 2005
$2.1M
Role of TET proteins in myeloid malignanciesR01CA151535 · NCI · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI RAO, ANJANA · 2012 to 2016
$1.8M
NCI NIH HHS R01 CA093152NCI NIH HHS R01 CA103846NCI NIH HHS R01 CA151535NCI NIH HHS R01 CA93152NCI NIH HHS T32 CA009216NHLBI NIH HHS R01 HL048801NIGMS NIH HHS DP1 GM105378NIGMS NIH HHS R01 GM088040
6 · The paper itself

Abstract

The ten-eleven translocation 2 gene (TET2) encodes a member of the TET family of DNA methylcytosine oxidases that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) to initiate the demethylation of DNA within genomic CpG islands. Somatic loss-of-function mutations of TET2 are frequently observed in human myelodysplastic syndrome (MDS), which is a clonal malignancy characterized by dysplastic changes of developing blood cell progenitors, leading to ineffective hematopoiesis. We used genome-editing technology to disrupt the zebrafish Tet2 catalytic domain. tet2(m/m) (homozygous for the mutation) zebrafish exhibited normal embryonic and larval hematopoiesis but developed progressive clonal myelodysplasia as they aged, culminating in myelodysplastic syndromes (MDS) at 24 months of age, with dysplasia of myeloid progenitor cells and anemia with abnormal circulating erythrocytes. The resultant tet2(m/m) mutant zebrafish lines show decreased levels of 5hmC in hematopoietic cells of the kidney marrow but not in other cell types, most likely reflecting the ability of other Tet family members to provide this enzymatic activity in nonhematopoietic tissues but not in hematopoietic cells. tet2(m/m) zebrafish are viable and fertile, providing an ideal model to dissect altered pathways in hematopoietic cells and, for small-molecule screens in embryos, to identify compounds with specific activity against tet2 mutant cells.

Indexed as

Disease Models, AnimalGene Expression RegulationAnimalsCatalytic DomainCell DifferentiationCpG IslandsDioxygenasesDNA-Binding ProteinsFlow CytometryGenotypeHematopoiesisHematopoietic Stem CellsHumansIn Situ HybridizationKidneyMutationDioxygenasesDNA-Binding ProteinsTET2 protein, zebrafishZebrafish Proteins

Identifiers

PMID25512612
PMCPMC4323485
OpenAlexW2110273215

What OpenQuestion holds

Textmetadata
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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.