Evidence map›Paper›PMID 32721103›Full record

Observational studyCancer reports (Hoboken, N.J.)2018

Aberrant DNA methylation at HOXA4 and HOXA5 genes are associated with resistance to imatinib mesylate among chronic myeloid leukemia patients.

Marjanu Hikmah Elias, Husin Azlan, Sarina Sulong, Abdul Aziz Baba, Ravindran Ankathil

Open access · greenAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Cancer reports (Hoboken, N.J.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
0.3field-weighted citation impact, top 39% 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, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Epigenetic alterations in Myeloid Malignancies.Advances in experimental medicine and biology · 2026
    Review
  4. Review
  5. Review
  6. Clinical applications of abnormal DNA methylation in chronic myeloid leukemia.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024
    Article
  7. Article
  8. Review
  9. Observational
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

5 authors at 4 institutions in 1 country.

Marjanu Hikmah EliasFaculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Nilai, Malaysia.ORCID 0000-0001-9343-7954
Husin AzlanHaemato-Oncology Unit, Department of Internal Medicine, Universiti Sains Malaysia Hospital, Kota Bharu, Malaysia.
Sarina SulongHuman Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
Abdul Aziz BabaInternational Medical University, Kuala Lumpur, Malaysia.
Ravindran AnkathilHuman Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
Universiti Sains Malaysia · MYHospital Universiti Sains Malaysia · MYIMU University · MYUniversiti Sains Islam Malaysia · MY

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImatinib mesylate is a molecularly targeted tyrosine kinase inhibitor drug. It is effectively used in the treatment of chronic myeloid leukemia (CML) patients. However, development of resistance to imatinib mesylate as a result of BCR-ABL dependent and BCR-ABL independent mechanisms has emerged as a daunting problem in the management of CML patients. Between these mechanisms, BCR-ABL independent mechanisms are still not robustly understood.

aimTo investigate the correlation of HOXA4 and HOXA5 promoter DNA hypermethylation with imatinib resistance among CML patients. METHODS AND

resultsSamples from 175 Philadelphia positive CML patients (83 good response and 92 BCR-ABL non-mutated imatinib resistant patients) were subjected to Methylation Specific High Resolution Melt Analysis for methylation levels quantification of the HOXA4 and HOXA5 promoter regions. Receiver operating characteristic curve analysis was done to elucidate the optimal methylation cut-off point followed by multiple logistic regression analysis. Log-Rank analysis was done to measure the overall survival difference between CML groups. The optimal methylation cut-off point was found to be at 62.5% for both HOXA4 and HOXA5. Chronic myeloid leukemia patients with ≥63% HOXA4 and HOXA5 methylation level were shown to have 3.78 and 3.95 times the odds, respectively, to acquire resistance to imatinib. However, overall survival of CML patients that have ≤62% and ≥ 63% methylation levels of HOXA4 and HOXA5 genes were found to be not significant (P-value = 0.126 for HOXA4; P-value = 0.217 for HOXA5).

conclusionHypermethylation of the HOXA4 and HOXA5 promoter is correlated with imatinib resistance and with further investigation, it could be a potential epigenetic biomarker in supplement to the BCR-ABL gene mutation in predicting imatinib treatment response among CML patients but could not be considered as a prognostic marker.

Indexed as

AdultBiomarkers, TumorDNA MethylationDrug Resistance, NeoplasmFemaleFusion Proteins, bcr-ablHomeodomain ProteinsHumansImatinib MesylateLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMaleMiddle AgedMutationTranscription Factorsabl-bcr fusion protein, humanBiomarkers, TumorFusion Proteins, bcr-ablHomeodomain ProteinsHOXA4 protein, humanHOXA5 protein, humanImatinib MesylateTranscription Factorschronic myeloid leukemiahigh‐resolution melt analysishypermethylationimatinib mesylateresistance

Identifiers

PMID32721103
PMCPMC7941502
OpenAlexW2883469809

What OpenQuestion holds

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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.