Gene expression analysis of paediatric acute lymphoblastic leukaemia

We addressed the clinical significance and mechanisms behind in vitro cellular responses to ionising radiation (IR)-induced DNA double strand breaks in 74 paediatric ALL patients. We found an apoptosis-resistant response in 36% of patients and an apoptosis-sensitive response in the remaining 64% of leukaemias. Global gene expression profiling of 11 apoptosis-resistant and 11 apoptosis-sensitive ALLs revealed abnormal up-regulation of multiple pro-survival pathways in response to IR in apoptosis-resistant leukaemias and differential post-transcriptional activation of the PI3-Akt pathway was observed in representative resistant cases. It is possible that abnormal pro-survival responses to DNA damage provide one of the mechanisms of primary resistance in ALL .

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Marston E, Weston V, Jesson J, Maina E, McConville C, Agathanggelou A, Skowronska A, Mapp K, Sameith K, Powell JE, Lawson S, Kearns P, Falciani F, Taylor M, Stankovic T