Hatfield Kimberley, Øyan Anne M, Ersvaer Elisabeth, Kalland Karl-Henning, Lassalle Philippe, Gjertsen Bjørn T, Bruserud Øystein
Section for Haematology, Institute of Medicine, University of Bergen, Norway.
Br J Haematol. 2009 Jan;144(1):53-68. doi: 10.1111/j.1365-2141.2008.07411.x. Epub 2008 Oct 30.
Bone marrow angiogenesis is suggested to play a role in the pathogenesis of acute myeloid leukaemia (AML) and endothelial cells may mediate chemosensitivity. This study investigated in vitro endothelial effects of coculture of microvascular endothelial cells (MVEC) with AML cells derived from 33 consecutive AML patients. A proliferation assay showed that (i) AML cells from the majority of patients examined increased endothelial cell proliferation, while cytokine neutralizing experiments had divergent effects on proliferation and (ii) the angiopoietin/Tie2 system was important for growth of AML cells, and angiopoietin-1 induced phosphorylation of signal transducers and activators of transcription (STAT) proteins in AML cells. Finally, gene expression profiling of MVEC cocultured with AML cells was conducted in non-contact cultures. Microarray analysis revealed that the majority of significantly expressed genes could be categorized into gene ontology terms involved in transcription, cellular organization and intracellular signalling. Our study indicates a role for the leukaemic-endothelium crosstalk in leukaemogenesis with enhancement of endothelial cell growth and increased AML cell proliferation possibly mediated by angiopoietin-1 and the STAT signalling pathway.
骨髓血管生成被认为在急性髓系白血病（AML）的发病机制中起作用，并且内皮细胞可能介导化疗敏感性。本研究调查了微血管内皮细胞（MVEC）与来自33例连续AML患者的AML细胞共培养的体外内皮细胞效应。增殖试验表明：（i）大多数受试患者的AML细胞增加了内皮细胞增殖，而细胞因子中和实验对增殖有不同影响；（ii）血管生成素/Tie2系统对AML细胞的生长很重要，血管生成素-1诱导AML细胞中信号转导子和转录激活子（STAT）蛋白的磷酸化。最后，在非接触培养中对与AML细胞共培养的MVEC进行基因表达谱分析。微阵列分析显示，大多数显著表达的基因可归类于参与转录、细胞组织和细胞内信号传导的基因本体学术语。我们的研究表明，白血病-内皮细胞相互作用在白血病发生中起作用，血管生成素-1和STAT信号通路可能介导内皮细胞生长增强和AML细胞增殖增加。
