Evidence map›Paper›PMID 33795806›Full record

ReviewCancer gene therapy2022

LEDGF/p75-mediated chemoresistance of mixed-lineage leukemia involves cell survival pathways and super enhancer activators.

Alessandro Canella, Siska Van Belle, Tine Brouns, Giovanni Nigita, Marianne S Carlon, Frauke Christ, Zeger Debyser

Open access · greenAbstract readReview
PubMed Publisher
In one paragraph

Review in Cancer gene therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

9 citing papers in PubMed, 11 citations in OpenAlex.

  1. Basic Virology.Advances in experimental medicine and biology · 2026
    Review
  2. PSIP1 promotes gefitinib resistance in lung adenocarcinoma by inducing the expression of WASF3 and its downstream ITGB3/AKT signaling.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Article
  3. Review
  4. Article
  5. Article
  6. Enhancer in cancer pathogenesis and treatment.Genetics and molecular biology · 2023
    Article
  7. Article
  8. Complex Relationships between HIV-1 Integrase and Its Cellular Partners.International journal of molecular sciences · 2022
    Review
  9. 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

7 authors at 3 institutions in 2 countries.

Alessandro CanellaLaboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Flanders, Belgium. alessandrocanella@ymail.com.ORCID http://orcid.org/0000-0002-0141-7399
Siska Van BelleLaboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Flanders, Belgium.
Tine BrounsLaboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Flanders, Belgium.
Giovanni NigitaDepartment of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0000-0001-8880-4334
Marianne S CarlonLaboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Flanders, Belgium.
Frauke ChristLaboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Flanders, Belgium.
Zeger DebyserLaboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Flanders, Belgium. zeger.debyser@kuleuven.be.ORCID http://orcid.org/0000-0002-3982-1565
KU Leuven · BERega Institute for Medical Research · BECancer Genetics (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

MLL is an aggressive subtype of leukemia with a poor prognosis that mostly affects pediatric patients. MLL-rearranged fusion proteins (MLLr) induce aberrant target gene expression resulting in leukemogenesis. MLL and its fusions are tethered to chromatin by LEDGF/p75, a transcriptional co-activator that specifically recognizes H3K36me2/3. LEDGF/p75 is ubiquitously expressed and associated with regulation of gene expression, autoimmune responses, and HIV replication. LEDGF/p75 was proven to be essential for leukemogenesis in MLL. Apart from MLL, LEDGF/p75 has been linked to lung, breast, and prostate cancer. Intriguingly, LEDGF/p75 interacts with Med-1, which co-localizes with BRD4. Both are known as co-activators of super-enhancers. Here, we describe LEDGF/p75-dependent chemoresistance of MLLr cell lines. Investigation of the underlying mechanism revealed a role of LEDGF/p75 in the cell cycle and in survival pathways and showed that LEDGF/p75 protects against apoptosis during chemotherapy. Remarkably, LEDGF/p75 levels also affected expression of BRD4 and Med1. Altogether, our data suggest a role of LEDGF/p75 in cancer survival, stem cell renewal, and activation of nuclear super enhancers.

Indexed as

Drug Resistance, NeoplasmLeukemiaBromodomain Containing ProteinsCell Cycle ProteinsCell SurvivalChildHumansIntercellular Signaling Peptides and ProteinsMaleNuclear ProteinsTranscription FactorsBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsIntercellular Signaling Peptides and Proteinslens epithelium-derived growth factorNuclear ProteinsTranscription Factors

Identifiers

PMID33795806
OpenAlexW3143887166

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.