Can Disruption of Circadian Rhythms Be Linked to Radiation-Induced Acute Myeloid Leukaemia?

Acute myeloid leukaemia (AML) remains a highly lethal malignancy with poor prognosis in adults above 60 years old and often occurs after radiation exposure. Emerging evidence suggests that circadian rhythm disruption, prevalent in shift workers, may contribute to cancer development. Clock genes (CGs) regulate fundamental cellular processes, including the DNA damage response (DDR), cell cycle progression, and haematopoiesis. In the absence of substantial experimental data, this review examines the potential pathways linking circadian clock dysregulation to radiation-induced AML (rAML) and evaluates how temporal disruption may modulate leukaemogenesis and radiation-induced effects. The evidence was synthesised on core clock components (BMAL1, CLOCK, PER, CRY, REV-ERB, ROR), their dysregulation in AML, and their roles in radiation response. Epigenetic and post-transcriptional regulatory mechanisms, including m⁶A RNA modification and sirtuin-mediated chromatin remodelling, were evaluated for their contribution to circadian-regulated DNA repair capacity. Multiple CGs demonstrated aberrant expression in AML, with BMAL1 showing tissue-specific dysregulation, and PER1/2/3 was consistently downregulated in peripheral blood. Clock proteins directly regulate DNA damage checkpoints through interactions with ATM/CHK2 and p53 pathways. Circadian disruption enhances inflammatory signalling, promotes accumulation of myeloid-derived suppressor cells, and accelerates immune senescence. Moreover, radiation exposure modulates CG expression, which may alter repair fidelity and increase leukaemogenic risk. Understanding these connections in the context of disrupted circadian rhythms could help identify at-risk populations and improve shift workplace health policies.