Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human paediatric acute lymphoblastic leukaemia

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Carmel McConville 

PROVIDER: E-GEOD-13280 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Stratification of pediatric ALL by in vitro cellular responses to DNA double-strand breaks provides insight into the molecular mechanisms underlying clinical response.

Marston Eliot E   Weston Victoria V   Jesson Jennifer J   Maina Esther E   McConville Carmel C   Agathanggelou Angelo A   Skowronska Anna A   Mapp Katie K   Sameith Katrin K   Powell Judith E JE   Lawson Sarah S   Kearns Pamela P   Falciani Francesco F   Taylor Malcolm M   Stankovic Tatjana T  

Blood 20081021 1

The molecular basis of different outcomes in pediatric acute lymphoblastic leukemia (ALL) remains poorly understood. We addressed the clinical significance and mechanisms behind in vitro cellular responses to ionizing radiation (IR)-induced DNA double-strand breaks in 74 pediatric patients with ALL. We found an apoptosis-resistant response in 36% of patients characterized by failure to cleave caspase-3, -7, -9, and PARP1 by 24 hours after IR and an apoptosis-sensitive response with the cleavage  ...[more]

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