Potential Candidate Genes for Therapeutic Targeting in Chronic Myeloid Leukemia: A Pilot Study

Document Type : Research Articles

Authors

1 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Imam Abdulrahaman Bin Faisal University, Dammam, Saudi Arabia.

2 Department of Internal Medicine, King Fahd Hospital of the University, Imam Abdulrahaman Bin Faisal University, Alkhobar, Saudi Arabia.

3 Department of Clinical Biochemistry, College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.

Abstract

Background: Chronic myeloid leukemia (CML) is a prevalent hematological malignancy known for the presence of the Philadelphia chromosome and activation of the BCR-Abl kinase activity. Although tyrosine kinase inhibitors are widely used as the standard treatment, resistance remains a concern among certain patients. This study aimed to investigate the gene expression profile of a group of CML patients in comparison to a control group in order to identify novel candidate genes associated with the disease. Methods: Whole transcriptome sequencing was performed, and gene expression levels were validated using quantitative real-time PCR. Additionally, single nucleotide and insertion/deletion variants were analyzed in the selected candidate genes among 10 CML patients and 4 healthy control subjects.Results: Analysis revealed a set of differentially expressed genes, whose up- or downregulation was further confirmed by qRT-PCR. Among the upregulated genes in the patient group were ribosomal protein like (RPL) members, specifically RPL9, RPL34, RPL36A, and RPL39, while downregulation was observed in CCDC170, LDB1, and SBF1 compared to the healthy subjects. Furthermore, gene variant studies identified novel genetic changes in these candidate genes, suggesting potential clinical significance in CML. Conclusions: This study highlights RPL9, RPL34, RPL36A, RPL39, CCDC170, LDB1, and SBF1 as potential targets in CML. Additionally, it underscores the importance of investigating these genes and their variants in larger cohort studies to assess their clinical significance in CML patients.

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