Evidence map›Paper›PMID 28074072›Full record

ArticleLeukemia2017

Targeting BET proteins improves the therapeutic efficacy of BCL-2 inhibition in T-cell acute lymphoblastic leukemia.

S Peirs, V Frismantas, F Matthijssens, W Van Loocke, T Pieters, N Vandamme, B Lintermans, M P Dobay, G Berx, B Poppe and 4 more

Open access · bronzeAbstract readComparative Study
PubMed Publisher
In one paragraph

Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Notch Inhibitors and BH3 Mimetics in T-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2024
    Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. BET Proteins as Attractive Targets for Cancer Therapeutics.International journal of molecular sciences · 2021
    Review
  18. Targeting epigenetic mechanisms to overcome venetoclax resistance.Biochimica et biophysica acta. Molecular cell research · 2021
    Review
  19. Article
  20. Co-Operativity between MYC and BCL-2 Pro-Survival Proteins in Cancer.International journal of molecular sciences · 2021
    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

14 authors at 4 institutions in 2 countries.

S PeirsCenter for Medical Genetics, Ghent University, Ghent, Belgium.ORCID 0000-0001-7036-1053
V FrismantasDepartment of Pediatric Oncology, Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.
F MatthijssensCenter for Medical Genetics, Ghent University, Ghent, Belgium.
W Van LoockeCenter for Medical Genetics, Ghent University, Ghent, Belgium.
T PietersCenter for Medical Genetics, Ghent University, Ghent, Belgium.
N VandammeCancer Research Institute Ghent (CRIG), Ghent, Belgium.
B LintermansCenter for Medical Genetics, Ghent University, Ghent, Belgium.
M P DobaySwiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
G BerxCancer Research Institute Ghent (CRIG), Ghent, Belgium.
B PoppeCenter for Medical Genetics, Ghent University, Ghent, Belgium.
S GoossensCenter for Medical Genetics, Ghent University, Ghent, Belgium.
B C BornhauserDepartment of Pediatric Oncology, Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.
J-P BourquinDepartment of Pediatric Oncology, Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.
P Van VlierbergheCenter for Medical Genetics, Ghent University, Ghent, Belgium.
Ghent University Hospital · BEUniversity Children's Hospital Zurich · CHGhent University · BESIB Swiss Institute of Bioinformatics · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Inhibition of anti-apoptotic BCL-2 (B-cell lymphoma 2) has recently emerged as a promising new therapeutic strategy for the treatment of a variety of human cancers, including leukemia. Here, we used T-cell acute lymphoblastic leukemia (T-ALL) as a model system to identify novel synergistic drug combinations with the BH3 mimetic venetoclax (ABT-199). In vitro drug screening in primary leukemia specimens that were derived from patients with high risk of relapse or relapse and cell lines revealed synergistic activity between venetoclax and the BET (bromodomain and extraterminal) bromodomain inhibitor JQ1. Notably, this drug synergism was confirmed in vivo using T-ALL cell line and patient-derived xenograft models. Moreover, the therapeutic benefit of this drug combination might, at least in part, be mediated by an acute induction of the pro-apoptotic factor BCL2L11 and concomitant reduction of BCL-2 upon BET bromodomain inhibition, ultimately resulting in an enhanced binding of BIM (encoded by BCL2L11) to BCL-2. Altogether, our work provides a rationale to develop a new type of targeted combination therapy for selected subgroups of high-risk leukemia patients.

Indexed as

Molecular Targeted TherapyAnimalsAntineoplastic Combined Chemotherapy ProtocolsAzepinesBcl-2-Like Protein 11Bridged Bicyclo Compounds, HeterocyclicBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorDrug SynergismFemaleGene Expression Regulation, NeoplasticHumansMiceMice, Inbred NODMice, SCIDAzepinesBCL2L11 protein, humanBcl-2-Like Protein 11BRD4 protein, humanBridged Bicyclo Compounds, HeterocyclicBromodomain Containing ProteinsCell Cycle Proteins(+)-JQ1 compoundNeoplasm ProteinsNuclear ProteinsProto-Oncogene Proteins c-bcl-2SulfonamidesTranscription FactorsTriazolesvenetoclax

Identifiers

PMID28074072
OpenAlexW2574795782

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.