Cancer genomics & proteomics · 2025
Gene Expression Insights into Cytarabine Resistance in Acute Myeloid Leukemia: The Role of Cytokines.
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Lee Chieh-Ming, Shih Yin-Hwa, Chen I-Chen, Shieh Tzong-Ming, Yeh Chung-Yu, Tseng Yu-Hsin
Аннотация
BACKGROUND/AIM: Cytarabine is the main chemotherapy agent used to treat acute myeloid leukemia (AML), but drug resistance remains a major challenge. Imbalances in cytokine secretion are known to play a role in the survival and proliferation of AML blast cells. While numerous studies have investigated cytokine secretion in AML, the precise role of cytokines in the pathogenesis of AML remains unclear. This study aimed to compare cytokine-related gene expression in parental and resistant HL60 cells and assess their prognostic relevance in AML.
MATERIALS AND METHODS: This study compared gene expression profiles of parental HL60 and R-HL60 cells by analyzing gene expression arrays. Further, the correlation between the differential expression genes (DEGs) and overall survival in patients with AML was obtained from the Cancer Genome Atlas (TCGA) database, and the expression of genes was validated by quantitative PCR (QPCR).
RESULTS: Our results showed that twenty-six genes involved in cytokine regulation were significantly different between HL60 and R-HL60 cells. The DEGs associated with cytokine production between parental HL60 and R-HL60 was subjected to a functional enrichment analysis by ShinyGO. The expression of BCL3, OAS3, RELB, AIM2, NFKB2, CLEC9A, and OAS2 involved in the regulation of cytokine production was associated with survival probability of AML patient in the TCGA database. Among them, the expression of BCL3, OAS3, RELB, AIM2, and NFKB2 genes in R-HL60 cells was higher than that in HL-60 cells.
CONCLUSION: This study identified key genes involved in cytokine dysregulation in cytarabine-resistant HL60 cells, providing potential targets for overcoming drug resistance in AML. These findings offer new avenues for the development of more effective therapies for relapsed or refractory AML patients.
MATERIALS AND METHODS: This study compared gene expression profiles of parental HL60 and R-HL60 cells by analyzing gene expression arrays. Further, the correlation between the differential expression genes (DEGs) and overall survival in patients with AML was obtained from the Cancer Genome Atlas (TCGA) database, and the expression of genes was validated by quantitative PCR (QPCR).
RESULTS: Our results showed that twenty-six genes involved in cytokine regulation were significantly different between HL60 and R-HL60 cells. The DEGs associated with cytokine production between parental HL60 and R-HL60 was subjected to a functional enrichment analysis by ShinyGO. The expression of BCL3, OAS3, RELB, AIM2, NFKB2, CLEC9A, and OAS2 involved in the regulation of cytokine production was associated with survival probability of AML patient in the TCGA database. Among them, the expression of BCL3, OAS3, RELB, AIM2, and NFKB2 genes in R-HL60 cells was higher than that in HL-60 cells.
CONCLUSION: This study identified key genes involved in cytokine dysregulation in cytarabine-resistant HL60 cells, providing potential targets for overcoming drug resistance in AML. These findings offer new avenues for the development of more effective therapies for relapsed or refractory AML patients.