Evidence map›Paper›PMID 23929215›Full record

ArticleLeukemia2014

BET protein inhibition shows efficacy against JAK2V617F-driven neoplasms.

B S Wyspiańska, A J Bannister, I Barbieri, J Nangalia, A Godfrey, F J Calero-Nieto, S Robson, I Rioja, J Li, M Wiese and 7 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

37 citing papers in PubMed, 68 citations in OpenAlex.

  1. Review
  2. Review
  3. Targeted Therapy for MPNs: Going Beyond JAK Inhibitors.Current hematologic malignancy reports · 2023
    Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Bromodomain biology and drug discovery.Nature structural & molecular biology · 2019
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Non-kinase targets of protein kinase inhibitors.Nature reviews. Drug discovery · 2017
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article
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

17 authors at 3 institutions in 1 country.

B S WyspiańskaGurdon Institute and Department of Pathology, University of Cambridge, Cambridge, UK.
A J BannisterGurdon Institute and Department of Pathology, University of Cambridge, Cambridge, UK.
I BarbieriGurdon Institute and Department of Pathology, University of Cambridge, Cambridge, UK.
J Nangalia1] Department of Haematology, Cambridge Institute for Medical Research and The Wellcome Trust and MRC Stem Cell Institute, University of Cambridge, Cambridge, UK [2] Addenbrooke's Hospital, Department of Haematology, University of Cambridge, Cambridge, UK.
A Godfrey1] Department of Haematology, Cambridge Institute for Medical Research and The Wellcome Trust and MRC Stem Cell Institute, University of Cambridge, Cambridge, UK [2] Addenbrooke's Hospital, Department of Haematology, University of Cambridge, Cambridge, UK.
F J Calero-NietoDepartment of Haematology, Cambridge Institute for Medical Research and The Wellcome Trust and MRC Stem Cell Institute, University of Cambridge, Cambridge, UK.
S RobsonGurdon Institute and Department of Pathology, University of Cambridge, Cambridge, UK.
I RiojaEpinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre, Stevenage, UK.
J Li1] Department of Haematology, Cambridge Institute for Medical Research and The Wellcome Trust and MRC Stem Cell Institute, University of Cambridge, Cambridge, UK [2] Addenbrooke's Hospital, Department of Haematology, University of Cambridge, Cambridge, UK.
M Wiese1] Gurdon Institute and Department of Pathology, University of Cambridge, Cambridge, UK [2] Department of Haematology, Cambridge Institute for Medical Research and The Wellcome Trust and MRC Stem Cell Institute, University of Cambridge, Cambridge, UK.
E Cannizzaro1] Gurdon Institute and Department of Pathology, University of Cambridge, Cambridge, UK [2] Department of Haematology, Cambridge Institute for Medical Research and The Wellcome Trust and MRC Stem Cell Institute, University of Cambridge, Cambridge, UK.
M A Dawson1] Gurdon Institute and Department of Pathology, University of Cambridge, Cambridge, UK [2] Department of Haematology, Cambridge Institute for Medical Research and The Wellcome Trust and MRC Stem Cell Institute, University of Cambridge, Cambridge, UK [3] Addenbrooke's Hospital, Department of Haematology, University of Cambridge, Cambridge, UK.
B HuntlyDepartment of Haematology, Cambridge Institute for Medical Research and The Wellcome Trust and MRC Stem Cell Institute, University of Cambridge, Cambridge, UK.
R K PrinjhaEpinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre, Stevenage, UK.
A R Green1] Department of Haematology, Cambridge Institute for Medical Research and The Wellcome Trust and MRC Stem Cell Institute, University of Cambridge, Cambridge, UK [2] Addenbrooke's Hospital, Department of Haematology, University of Cambridge, Cambridge, UK.
B GottgensDepartment of Haematology, Cambridge Institute for Medical Research and The Wellcome Trust and MRC Stem Cell Institute, University of Cambridge, Cambridge, UK.ORCID 0000000163025705
T KouzaridesGurdon Institute and Department of Pathology, University of Cambridge, Cambridge, UK.
Wellcome/MRC Cambridge Stem Cell Institute · GBUniversity of Cambridge · GBGlaxoSmithKline (United Kingdom) · GB

Funding

Biotechnology and Biological Sciences Research CouncilCancer Research UK 10827Cancer Research UK 12765Cancer Research UK 17001Medical Research Council MC_PC_12009National Centre for the Replacement, Refinement and Reduction of Animals in Research G0900729/1Wellcome Trust 079249Wellcome Trust 092096Wellcome Trust 100140
6 · The paper itself

Abstract

Small molecule inhibition of the BET family of proteins, which bind acetylated lysines within histones, has been shown to have a marked therapeutic benefit in pre-clinical models of mixed lineage leukemia (MLL) fusion protein-driven leukemias. Here, we report that I-BET151, a highly specific BET family bromodomain inhibitor, leads to growth inhibition in a human erythroleukemic (HEL) cell line as well as in erythroid precursors isolated from polycythemia vera patients. One of the genes most highly downregulated by I-BET151 was LMO2, an important oncogenic regulator of hematopoietic stem cell development and erythropoiesis. We previously reported that LMO2 transcription is dependent upon Janus kinase 2 (JAK2) kinase activity in HEL cells. Here, we show that the transcriptional changes induced by a JAK2 inhibitor (TG101209) and I-BET151 in HEL cells are significantly over-lapping, suggesting a common pathway of action. We generated JAK2 inhibitor resistant HEL cells and showed that these retain sensitivity to I-BET151. These data highlight I-BET151 as a potential alternative treatment against myeloproliferative neoplasms driven by constitutively active JAK2 kinase.

Indexed as

Cell Line, TumorChromatin ImmunoprecipitationHematologic NeoplasmsHumansJanus Kinase 2Myeloproliferative DisordersOncogene ProteinsReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionJanus Kinase 2Oncogene Proteins

Identifiers

PMID23929215
OpenAlexW2089259281

What OpenQuestion holds

Textmetadata
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.