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 . Keywords: Gene expression profiling; response to irradiation 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.

本研究针对74例儿童急性淋巴细胞白血病（Acute Lymphoblastic Leukemia, ALL）患者，探讨了体外细胞对电离辐射（Ionising Radiation, IR）诱导的DNA双链断裂（DNA double strand breaks）产生应答的临床意义与作用机制。研究发现，36%的患者表现为凋亡抵抗应答，剩余64%的白血病样本呈现凋亡敏感应答。对11例凋亡抵抗型与11例凋亡敏感型ALL样本进行全基因表达谱分析后发现，凋亡抵抗型白血病经电离辐射刺激后，多条促存活通路出现异常上调；且在典型耐药病例中，观察到PI3-Akt通路存在差异性转录后激活现象。针对DNA损伤的异常促存活应答，可能是急性淋巴细胞白血病原发性耐药的潜在机制之一。
关键词：基因表达谱分析；辐射应答
本研究采用Affymetrix HG_U133A（GPL96）平台，对22例B细胞前体ALL肿瘤样本（11例对电离辐射诱导的DNA损伤产生应答，11例耐药）在接受5 Gy电离辐射照射前及照射后8小时进行了分析。