Evidence map›Paper›PMID 24370659›Full record

ReviewEuropean journal of clinical pharmacology2014

Pharmacogenetics of methotrexate in acute lymphoblastic leukaemia: why still at the bench level?

Sunitha Kodidela, Pradhan Suresh Chandra, Biswajit Dubashi

Abstract readReview
PubMed Publisher
In one paragraph

Review in European journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 8% 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, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Association ofCurrent issues in molecular biology · 2024
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Association ofGenes · 2020
    Article
  12. Article
  13. Review
  14. Ginger extract has anti-leukemia and anti-drug resistant effects on malignant cells.Journal of cancer research and clinical oncology · 2019
    Article
  15. Article
  16. Renal Function and Plasma Methotrexate Concentrations Predict Toxicities in Adults Receiving High-Dose Methotrexate.Medical science monitor : international medical journal of experimental and clinical research · 2018
    Article
  17. Review
  18. Article
  19. Gene polymorphisms in the folate metabolism and their association with MTX-related adverse events in the treatment of ALL.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015
    Review
  20. 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

3 authors at 1 institution in 1 country.

Sunitha KodidelaDepartment of Pharmacology, Jawaharlal Institute of Medical Education and Research (JIPMER), Puducherry, India, kodidela.sunitha@gmail.com.
Pradhan Suresh Chandra
Biswajit Dubashi
Jawaharlal Institute of Post Graduate Medical Education and Research · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe antifolate drug methotrexate (MTX) was introduced into clinical practice about 60 years ago and remains an important component of different acute lymphoblastic leukemia (ALL) treatment protocols. It acts by inhibiting several enzymes in the folate pathway, thereby resulting in the disruption of folate homeostasis. To date, treatment regimens have not been personalized despite there being experimental evidence that gene polymorphisms of folate metabolizing enzymes affect MTX response. The aim of this review was to evaluate the influence of genetic polymorphisms of the enzymes involved in the MTX pathway on ALL treatment outcomes and identify factors underlining the failure to personalize MTX therapy.

methodsWe conducted a literature search in PUBMED and Google Scholar using the following key words: methotrexate, polymorphism, acute lymphoblastic leukemia, pharmacogenetics, pharmacogenomics and personalized medicine.

resultsThe reasons for the failure to personalize MTX therapy may be due to (1) most studies involving single-center, small-sized cohorts, (2) differences in MTX dose across different protocols, (3) failure to consider minimal residual disease as a risk factor for post-induction treatment, (4) differences in outcome criteria between studies and (5) failure to consider the folate levels of a patient before initiation of MTX therapy. Although high-throughput techniques allow the mapping of thousands of genetic polymorphisms in a single run, it remains a major challenge to dissect out folate-metabolizing enzymes which have a high impact on the efficacy and toxicity of MTX and which, therefore, could be the targets for intervention.

conclusionsProspective pharmacogenetic studies which consider all of the above-mentioned factors should be undertaken to facilitate the design of personalized MTX treatment for ALL patients.

Indexed as

Antimetabolites, AntineoplasticHumansMethotrexatePharmacogeneticsPolymorphism, GeneticPrecision MedicinePrecursor Cell Lymphoblastic Leukemia-LymphomaAntimetabolites, AntineoplasticMethotrexate

Identifiers

PMID24370659
OpenAlexW2059980136

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.