Proteomic analysis identifies differentially expressed proteins in AML1/ETO acute myeloid leukemia cells treated with DNMT inhibitors azacitidine and decitabine
Proteomic analysis identifies differentially expressed proteins in AML1/ETO acute myeloid leukemia cells treated with DNMT inhibitors azacitidine and decitabine
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DOI：
10.1016/j.leukres.2011.11.024
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发表时间：
2012-05-01
影响因子：
2.7
通讯作者：
Santini, Valeria
中科院分区：
文献类型：
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作者：
Buchi, Francesca;Spinelli, Elena;Santini, Valeria
阿扎胞苷和地西他滨是 DNA 甲基转移酶抑制剂，用于治疗骨髓增生异常综合征和急性髓系白血病。为了进一步表征这两种药物之间的不同机制，使用二维电泳分析了未经处理或用任一药物处理的白血病细胞的细胞提取物。通过 MALDI-TOF/TOF-MS 鉴定了许多差异表达的蛋白质。两种药物均仅通过阿扎胞苷、TCP1 和 hnRNP A2/B1 降低亲环素 A、过氧化氢酶、核磷蛋白和 PCNA；地西他滨的 α-烯醇化酶和 Peroxiredoxin-1。有趣的是，促炎蛋白亲环蛋白 A 的表达（也被认为是细胞坏死的标志物）受到地西他滨的刺激。最后，对数据进行全面的通路分析强调了已识别的蛋白质和潜在效应物之间的关系。 (C) 2011 Elsevier Ltd. 保留所有权利。
Azacitidine and decitabine are DNA methyltransferase inhibitors used to treat myelodysplastic syndromes and acute myeloid leukemias. To further characterize different mechanisms between these two agents, cellular extracts from leukemic cells untreated or treated with either drug were analyzed using 2D electrophoresis. Numerous differentially expressed proteins were identified with MALDI-TOF/TOF-MS. Cyclophilin A, Catalase, Nucleophosmin and PCNA were decreased exclusively by azacitidine, TCP1 and hnRNP A2/B1 by both drugs; alpha-Enolase and Peroxiredoxin-1 by decitabine. Interestingly, the expression of the proinflammatory protein Cyclophilin A, also suggested as marker of cell necrosis, was stimulated by decitabine. Finally, a comprehensive pathway analysis of data highlighted a relationship between the identified proteins and potential effectors. (C) 2011 Elsevier Ltd. All rights reserved.