Evidence map›Paper›PMID 33099992›Full record

ReviewHaematologica2021

Emerging epigenetic therapeutics for myeloid leukemia: modulating demethylase activity with ascorbate.

Andrew B Das, Carlos C Smith-Díaz, Margreet C M Vissers

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

21 citing papers in PubMed, 24 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. The Epigenetic Role of Vitamin C in Neurodevelopment.International journal of molecular sciences · 2022
    Review
  11. Review
  12. Review
  13. Article
  14. Structure and Function of TET Enzymes.Advances in experimental medicine and biology · 2022
    Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  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

3 authors at 1 institution in 1 country.

Andrew B DasDepartment of Pathology and Biomedical Science, University of Otago, Christchurch. andrew.das@otago.ac.nz.
Carlos C Smith-DíazDepartment of Pathology and Biomedical Science, University of Otago, Christchurch.
Margreet C M VissersDepartment of Pathology and Biomedical Science, University of Otago, Christchurch.
University of Otago · NZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The past decade has seen a proliferation of drugs that target epigenetic pathways. Many of these drugs were developed to treat acute myeloid leukemia, a condition in which dysregulation of the epigenetic landscape is well established. While these drugs have shown promise, critical issues persist. Specifically, patients with the same mutations respond quite differently to treatment. This is true even with highly specific drugs that are designed to target the underlying oncogenic driver mutations. Furthermore, patients who do respond may eventually develop resistance. There is now evidence that epigenetic heterogeneity contributes, in part, to these issues. Cancer cells also have a remarkable capacity to 'rewire' themselves at the epigenetic level in response to drug treatment, and thereby maintain expression of key oncogenes. This epigenetic plasticity is a promising new target for drug development. It is therefore important to consider combination therapy in cases in which both driver mutations and epigenetic plasticity are targeted. Using ascorbate as an example of an emerging epigenetic therapeutic, we review the evidence for its potential use in both of these modes. We provide an overview of 2-oxoglutarate dependent dioxygenases with DNA, histone and RNA demethylase activity, focusing on those which require ascorbate as a cofactor. We also evaluate their role in the development and maintenance of acute myeloid leukemia. Using this information, we highlight situations in which the use of ascorbate to restore 2-oxoglutarate dependent dioxygenase activity could prove beneficial, in contrast to contexts in which targeted inhibition of specific enzymes might be preferred. Finally, we discuss how these insights could be incorporated into the rational design of future clinical trials.

Indexed as

EpigenomicsLeukemia, Myeloid, AcuteCarcinogenesisEpigenesis, GeneticHistonesHumansHistones

Identifiers

PMID33099992
PMCPMC7776339
OpenAlexW3093576128

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.