E-GEOD-13280 - Transcription profiling of human paediatric acute lymphoblastic leukaemia
Submitted on 20 October 2008, released on 13 November 2008, last updated on 27 March 2012
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 . Experiment Overall Design: Twenty two B-precursor ALL tumours (11 responsive to IR-induced DNA damage and 11 resistant) were analysed before and 8 hours after exposure to 5 Gy IR, using the Affymetrix HG_U133A (GPL96) platform.
transcription profiling by array, unknown experiment type
Stratification of paediatric ALL by in vitro cellular responses to DNA double strand breaks provides insight into the molecular mechanisms underlying clinical response. Weston Marston, Maina Jesson, Agathanggelou McConville, Mapp Skowronska, Powell Sameith, Kearns Lawson, Taylor Falciani, Stankovic.