Related Experiment Video
Updated: Nov 4, 2025
A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
Screening and identification of key genes in imatinib-resistant chronic myelogenous leukemia cells: a bioinformatics
Hong Zhang1, Peiran Wang2, Ting Song2
1State Key Laboratory of Fine Chemicals, School of Life Science and Technology, Dalian University of Technology, Dalian, People's Republic of China.
Background:
Chronic myelogenous leukemia (CML) is one of the most common cancers in the world. Imatinib is one of the most effective therapeutic strategies to inhibit the BCR-ABL tyrosine Kinase in patients with CML, but resistance is increasingly encountered.
Material And Methods:
Microarray data GSE7114, GSE92624 and GSE97562 were downloaded and analyzed from Gene Expression Omnibus (GEO) to identify the candidate genes in the imatinib-resistant CML cells. The differentially expressed genes (DEGs) were appraised, and the protein-protein interaction (PPI) network was created by using STRING and Cytoscape.
Results:
We screened a total of 217 DEGs, including 151 upregulated genes and 66 downregulated genes. The enriched functions and pathways of genes include insulin-like growth factor I binding, cysteine-type endopeptidase inhibitor activity involved in apoptotic process, cell adhesion, positive regulation of nitric oxide biosynthetic process and hematopoietic cell lineage. Nine hub genes were appraised and Gene Ontology enrichment analysis revealed that these genes are mainly enriched in cell cycle, peptidase inhibitor activity and cell division. Several genes such as BIRC5, CCNE2 and MCM4 were identified in survival analysis and these genes alteration are significantly associated with worse overall survival and disease-free survival.
Conclusions:
These genes have the potential to become surrogate markers for a clinical evaluation of imatinib-resistant CML patients. Our results provide potential target genes for diagnosis and treatment of imatinib-resistant CML patients.
Insights
New genes identified may help diagnose and treat imatinib-resistant chronic myelogenous leukemia (CML). These findings offer potential biomarkers for imatinib-resistant CML patients, improving clinical evaluation and therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Chronic myelogenous leukemia (CML) is a prevalent cancer globally.
- Imatinib is a key therapy targeting BCR-ABL tyrosine kinase in CML.
- Acquired resistance to imatinib poses a significant clinical challenge.
Purpose of the Study:
- To identify novel genes associated with imatinib resistance in CML.
- To explore potential diagnostic and therapeutic targets for resistant CML.
- To analyze gene expression patterns in imatinib-resistant CML cells.
Main Methods:
- Analysis of microarray datasets (GSE7114, GSE92624, GSE97562) from the Gene Expression Omnibus (GEO).
- Identification and appraisal of differentially expressed genes (DEGs).
- Construction of a protein-protein interaction (PPI) network using STRING and Cytoscape.
Main Results:
- A total of 217 DEGs were identified (151 upregulated, 66 downregulated).
- Enriched functions include insulin-like growth factor I binding and apoptotic processes.
- Nine hub genes, including BIRC5, CCNE2, and MCM4, were linked to poorer survival outcomes in CML patients.
Conclusions:
- Identified genes show potential as surrogate markers for clinical evaluation of imatinib-resistant CML.
- These genes represent promising targets for the diagnosis and treatment of imatinib-resistant CML.
- The study provides a foundation for developing new therapeutic strategies against resistant CML.
