Overexpression of the GABBR۱ gene in AML patients: A correlation with chemoresistance

Acute Myeloid Leukemia (AML) originates from the bone marrow and quickly moves into the blood. AML remains a significant health challenge worldwide, particularly affecting older adults. While it is a relatively rare form of cancer, its aggressive nature and complex treatment requirements makes it a critical focus of ongoing medical research. Resistance to chemotherapy drugs is the main reason for treatment failure in AML. Improved understanding of its genetic basis and advancements in targeted therapies could offer hope for better outcomes and increased survival rates in the future. Evidence indicated the importance of the gamma-aminobutyric acid B receptor, ۱ (GABBR۱) gene as a biomarker in various cancers. To date, its role in AML and its relationship with drug resistance in cancer have not been investigated. Our previous in-silico analysis results illustrated a strong positive correlation between dysregulation of the GABBR۱ gene and resistance to treatment in AML patients. The aim of the study was to validate the function of the GABBR۱ gene in predicting resistance to standard chemotherapy and targeted therapies in AML patients. Methods: We conducted a comparative analysis of GABBR۱ mRNA expression levels in thirty-one fresh bone marrow samples from AML patients. The cohort included both drug-resistant and drug-sensitive individuals. Quantitative real-time PCR (qRT-PCR) was employed to measure the expression levels of GABBR۱. Statistical analyses were performed to evaluate the significance of the differences observed. Results: Our results revealed a significant increase in the level of the GABBR۱ mRNA in AML drug-resistant patients compared to those with drug-sensitive (P-value=۰.۰۰۰۷). Furthermore, the results for area under the curve (AUC) analysis for the GABBR۱ gene was ۰.۸۲, which indicates its high potential as prognostic molecular marker. Conclusion: The data demonstrated that the upregulation of the GABBR۱ gene played a significant role in the mechanism of resistance to chemotherapy of AML.

کلیدواژه ها:

Acute Myeloid Leukemia ، Drug-resistance ، Drug-sensitive ، Prognostic biomarker ، GABBR۱