Evidence map›Paper›PMID 26304963›Full record

ArticleThe Journal of experimental medicine2015

A novel mouse model identifies cooperating mutations and therapeutic targets critical for chronic myeloid leukemia progression.

George Giotopoulos, Louise van der Weyden, Hikari Osaki, Alistair G Rust, Paolo Gallipoli, Eshwar Meduri, Sarah J Horton, Wai-In Chan, Donna Foster, Rab K Prinjha and 6 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

24 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Case Report:Frontiers in oncology · 2023
    Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 10 institutions in 5 countries.

George GiotopoulosDepartment of Haematology, Cambridge Institute for Medical Research and Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0XY, England, UK Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1TN, England, UK.
Louise van der WeydenExperimental Cancer Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Hikari OsakiDepartment of Haematology, Cambridge Institute for Medical Research and Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0XY, England, UK Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1TN, England, UK.
Alistair G RustExperimental Cancer Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK Tumour Profiling Unit, The Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, England, UK.
Paolo GallipoliDepartment of Haematology, Cambridge Institute for Medical Research and Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0XY, England, UK Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1TN, England, UK.
Eshwar MeduriDepartment of Haematology, Cambridge Institute for Medical Research and Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0XY, England, UK Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1TN, England, UK.
Sarah J HortonDepartment of Haematology, Cambridge Institute for Medical Research and Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0XY, England, UK Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1TN, England, UK.
Wai-In ChanDepartment of Haematology, Cambridge Institute for Medical Research and Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0XY, England, UK Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1TN, England, UK.
Donna FosterDepartment of Haematology, Cambridge Institute for Medical Research and Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0XY, England, UK Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1TN, England, UK.
Rab K PrinjhaEpinova DPU, GlaxoSmithKline, Medicines Research Centre, Stevenage SG1 2NY, England, UK.
John E PimandaLowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.
Daniel G TenenCancer Science Institute, National University of Singapore, Singapore 119077 Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115.
George S VassiliouHaematological Cancer Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, England, UK.
Steffen KoschmiederDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, 52062 Aachen, Germany.
David J AdamsExperimental Cancer Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Brian J P HuntlyDepartment of Haematology, Cambridge Institute for Medical Research and Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0XY, England, UK Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1TN, England, UK bjph2@cam.ac.uk.
University of Cambridge · GBWellcome Sanger Institute · GBMedical Research Council · GBWellcome/MRC Cambridge Stem Cell Institute · GBAddenbrooke's Hospital · GBGlaxoSmithKline (United Kingdom) · GBHarvard University · USInstitute of Cancer Research · GBRWTH Aachen University · DEUNSW Sydney · AU

Funding

Cancer Research UK 13031Medical Research Council MR/M010392/1Wellcome Trust 095663Wellcome Trust 97922Worldwide Cancer Research 14-1069
6 · The paper itself

Abstract

The introduction of highly selective ABL-tyrosine kinase inhibitors (TKIs) has revolutionized therapy for chronic myeloid leukemia (CML). However, TKIs are only efficacious in the chronic phase of the disease and effective therapies for TKI-refractory CML, or after progression to blast crisis (BC), are lacking. Whereas the chronic phase of CML is dependent on BCR-ABL, additional mutations are required for progression to BC. However, the identity of these mutations and the pathways they affect are poorly understood, hampering our ability to identify therapeutic targets and improve outcomes. Here, we describe a novel mouse model that allows identification of mechanisms of BC progression in an unbiased and tractable manner, using transposon-based insertional mutagenesis on the background of chronic phase CML. Our BC model is the first to faithfully recapitulate the phenotype, cellular and molecular biology of human CML progression. We report a heterogeneous and unique pattern of insertions identifying known and novel candidate genes and demonstrate that these pathways drive disease progression and provide potential targets for novel therapeutic strategies. Our model greatly informs the biology of CML progression and provides a potent resource for the development of candidate therapies to improve the dismal outcomes in this highly aggressive disease.

Indexed as

Gene Expression Regulation, LeukemicAnimalsDNA Transposable ElementsFusion Proteins, bcr-ablGenes, mybHematopoietic Stem CellsHumansLeukemia, ExperimentalLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMice, TransgenicMolecular Targeted TherapyMutagenesis, InsertionalMutationTumor Cells, CulturedVascular Endothelial Growth Factor CDNA Transposable ElementsFusion Proteins, bcr-ablVascular Endothelial Growth Factor Cvascular endothelial growth factor C, mouse

Identifiers

PMID26304963
PMCPMC4577832
OpenAlexW2116641711

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

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.