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Updated: Sep 29, 2025
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
A Systematic Review of Candidate miRNAs, Its Targeted Genes and Pathways in Chronic Myeloid Leukemia-An Integrated
Marjanu Hikmah Elias1, Syarifah Faezah Syed Mohamad1,2, Nazefah Abdul Hamid1
1Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Nilai, Malaysia.
Abstract:
Chronic myeloid leukaemia is blood cancer due to a reciprocal translocation, resulting in a BCR-ABL1 oncogene. Although tyrosine kinase inhibitors have been successfully used to treat CML, there are still cases of resistance. The resistance occurred mainly due to the mutation in the tyrosine kinase domain of the BCR-ABL1 gene. However, there are still many cases with unknown causes of resistance as the etiopathology of CML are not fully understood. Thus, it is crucial to figure out the complete pathogenesis of CML, and miRNA can be one of the essential pathogeneses. The objective of this study was to systematically review the literature on miRNAs that were differentially expressed in CML cases. Their target genes and downstream genes were also explored. An electronic search was performed via PubMed, Scopus, EBSCOhost MEDLINE, and Science Direct. The following MeSH (Medical Subject Heading) terms were used: chronic myeloid leukaemia, genes and microRNAs in the title or abstract. From 806 studies retrieved from the search, only clinical studies with in-vitro experimental evidence on the target genes of the studied miRNAs in CML cells were included. Two independent reviewers independently scrutinised the titles and abstracts before examining the eligibility of studies that met the inclusion criteria. Study design, sample size, sampling type, and the molecular method used were identified for each study. The pooled miRNAs were analysed using DIANA tools, and target genes were analysed with DAVID, STRING and Cytoscape MCODE. Fourteen original research articles on miRNAs in CML were included, 26 validated downstream genes and 187 predicted target genes were analysed and clustered into 7 clusters. Through GO analysis, miRNAs' target genes were localised throughout the cells, including the extracellular region, cytosol, and nucleus. Those genes are involved in various pathways that regulate genomic instability, proliferation, apoptosis, cell cycle, differentiation, and migration of CML cells.
Insights
MicroRNAs (miRNAs) play a crucial role in chronic myeloid leukemia (CML) pathogenesis and drug resistance. This review explores differentially expressed miRNAs and their targets, offering insights into CML development and treatment strategies.
Area of Science:
- Hematology
- Molecular Biology
- Genetics
Background:
- Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by the BCR-ABL1 oncogene.
- While tyrosine kinase inhibitors (TKIs) are effective, drug resistance remains a challenge, often linked to BCR-ABL1 mutations, but other factors are implicated.
- The complete pathogenesis of CML is not fully understood, highlighting the need to explore novel regulatory mechanisms like microRNAs (miRNAs).
Approach:
- A systematic literature review was conducted using PubMed, Scopus, EBSCOhost MEDLINE, and Science Direct.
- MeSH terms included "chronic myeloid leukaemia," "genes," and "microRNAs."
- Included studies were clinical with in-vitro evidence on miRNA target genes in CML cells, with data analyzed using DIANA, DAVID, STRING, and Cytoscape MCODE.
Key Points:
- Fourteen original research articles were included, analyzing 187 predicted and 26 validated target genes across 7 clusters.
- Gene Ontology (GO) analysis revealed miRNA targets are located in various cellular compartments (extracellular, cytosol, nucleus).
- These target genes are involved in critical cellular processes including genomic instability, proliferation, apoptosis, cell cycle, differentiation, and migration in CML cells.
Conclusions:
- MicroRNAs are significantly involved in the pathogenesis of chronic myeloid leukemia.
- Understanding miRNA dysregulation and their target genes provides crucial insights into CML development and potential therapeutic strategies.
- Further research into miRNA roles could elucidate unknown mechanisms of CML resistance and inform novel treatment approaches.
