Anaesthetics influence leukaemia cell biology and malignancy: Mechanisms and Implications

Acute lymphoblastic leukaemia (ALL) is the most common type of cancer in children. During ALL treatments, general anaesthetics are often used on patients undergoing painful procedures. General anaesthetics have been shown to influence cancer cell biology in solid cancer models. However, no study has been published regarding the effects of anaesthetics on leukaemia. To further our understanding, the objective of this thesis is to compare the effects of two commonly used general anaesthetics (intravenous: propofol and inhalational: sevoflurane) on ALL in vitro and in vivo. Propofol and sevoflurane reduce proliferation, CXCR4 expression, osteopontin (OPN) secretion and migration of leukaemia cells in vitro. In addition, both anaesthetics reduce homing and migration of leukaemia cells in vivo. Upon further investigation, hypoxia-inducible factor-1 alpha (HIF-1α) is responsible for induced molecular changes in leukaemia cells. HIF-1α is reduced by propofol in a dose-dependent manner, and its effect is relatively short-term (