Dysregulation of circadian clock gene BMAL1 and cell cycle regulator WEE1 in pediatric AML.
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BACKGROUND: Growing evidence indicates that dysregulation of circadian clock genes and cell cycle regulators plays a role in the pathogenesis of malignancies. BMAL1, a core circadian clock gene, and WEE1, a key regulator of the G2/M cell cycle checkpoint, are involved in controlling cell proliferation and maintaining genomic stability. The present study aimed to evaluate the expression pattern of these two genes in children with acute myeloid leukemia. METHODS: In this study, bone marrow samples from 40 newly diagnosed pediatric AML patients and 20 non-malignant control subjects were analyzed. The expression levels of BMAL1 and WEE1 were measured using real-time quantitative PCR. The association between gene expression and hematological parameters, including white blood cell count, hemoglobin, platelet count, and blast percentage, was also assessed. RESULTS: The expression levels of both BMAL1 and WEE1 were significantly lower in AML patients compared with the control group (P < 0.001). The relative expression levels of BMAL1 and WEE1 were 0.18 and 0.31-fold of the control group, respectively. In addition, a significant negative correlation was observed between BMAL1 expression and white blood cell count (r = -0.440, P = 0.004) as well as blast percentage (r = -0.418, P = 0.007). In contrast, WEE1 expression showed no significant correlation with any of the evaluated hematological parameters. CONCLUSION: The significant downregulation of BMAL1 and WEE1 in pediatric AML suggests a potential role of disrupted circadian clock and cell cycle regulatory pathways in the pathogenesis of this disease.