Molecular recognition of acute myeloid leukemia using aptamers.

Molecular recognition of acute myeloid leukemia using aptamers.
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DOI:
10.1038/leu.2008.335
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发表时间:
2009-02
期刊:
影响因子:
11.4
通讯作者:
--
中科院分区:
医学1区
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--
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细胞表面蛋白在癌症发病机制中发挥重要作用。全面了解肿瘤细胞表面蛋白表达模式,从而了解肿瘤细胞的发病机制,依赖于针对这些蛋白的分子探针。为了有效地用于肿瘤诊断、分类和治疗,此类探针将能够特异性结合靶向肿瘤细胞。分子适体,设计的DNA/RNA探针,可以通过识别蛋白质,肽和其他小分子以高亲和力和特异性来解决这一挑战。通过一种称为cell-SELEX的过程,我们使用活的急性髓性白血病(AML)细胞来选择一组DNA适体,这些DNA适体可以识别解离常数(Kds)在纳摩尔范围内的急性髓性白血病细胞。有趣的是,与两种对照细胞系(K562和NB 4)相比,一种适体(KH 1C 12)对靶AML细胞系(HL 60)显示出显著的选择性,并且可以识别正常骨髓抽吸物的复杂混合物中的靶细胞。另外两种适体KK 1B 10和KK 1D 04识别与单核细胞分化相关的靶标。我们的研究表明,所选择的适体可以用作进一步了解肿瘤细胞表面蛋白表达模式的分子工具,从而为白血病及其亚型的有效分子分析提供基础。
Cell surface proteins can play important roles in cancer pathogenesis. Comprehensive understanding of the surface protein expression patterns of tumor cells and, consequently, the pathogenesis of tumor cells, depends on molecular probes against these proteins. To be effectively used for tumor diagnosis, classification and therapy, such probes would be capable of specific binding to targeted tumor cells. Molecular aptamers, designer DNA/RNA probes, can address this challenge by recognizing proteins, peptides and other small molecules with high affinity and specificity. Through a process known as cell-SELEX, we used live acute myeloid leukemia (AML) cells to select a group of DNA aptamers that can recognize acute myeloid leukemia cells with dissociation constants (Kds) in the nanomolar range. Interestingly, one aptamer (KH1C12), compared with two control cell lines (K562 and NB4), showed significant selectivity to the target AML cell line (HL60) and could recognize the target cells within a complex mixture of normal bone marrow aspirates. The other two aptamers KK1B10 and KK1D04 recognize targets associated with monocytic differentiation. Our studies demonstrate that the selected aptamers can be used as a molecular tool for further understanding surface protein expression patterns on tumor cells and thus providing a foundation for effective molecular analysis of leukemia and its subcategories.
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