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首页> 外文期刊>Molecular cancer therapeutics >A novel treatment strategy targeting Aurora kinases in acute myelogenous leukemia.
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A novel treatment strategy targeting Aurora kinases in acute myelogenous leukemia.

机译：一种针对急性骨髓性白血病中Aurora激酶的新型治疗策略。

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The Aurora kinases play an important role in chromosome alignment, segregation, and cytokinesis during mitosis. Aberrant expression of these kinases occurs in solid tumors and is associated with aneuploidy and carcinogenesis. We found in this study that Aurora kinase A and B were aberrantly expressed in a variety of types of human leukemia cell lines (n = 15, e.g., PALL-1, PALL-2, HL-60, NB4, MV4-11, etc.), as well as freshly isolated leukemia cells from individuals with acute myelogenous leukemia (n = 44) compared with bone marrow mononuclear cells from healthy volunteers (n = 11), as measured by real-time PCR. ZM447439 is a novel selective Aurora kinase inhibitor. The compound induced growth inhibition, caused accumulation of cells with 4N/8N DNA content, and mediated apoptosis of human leukemia cells as measured by thymidine uptake, cell cycle analysis, and annexin V staining, respectively. Especially profound growth inhibition occurred with the PALL-1 and PALL-2 cells, which possess wild-type p53 gene. In contrast, ZM447439 did not inhibit clonogenic growth of myeloid committed stem cells harvested from healthy normal volunteers. Taken together, inhibition of Aurora kinases may be a promising treatment strategy for individuals with leukemia.
机译：Aurora激酶在有丝分裂过程中的染色体排列，分离和胞质分裂中起重要作用。这些激酶的异常表达发生在实体瘤中，并与非整倍性和致癌作用有关。在这项研究中，我们发现Aurora激酶A和B在多种类型的人类白血病细胞系中异常表达（n = 15，例如PALL-1，PALL-2，HL-60，NB4，MV4-11等），以及通过实时PCR测定的急性骨髓性白血病（n = 44）与健康志愿者的骨髓单核细胞（n = 11）的新鲜分离的白血病细胞。 ZM447439是新型的选择性Aurora激酶抑制剂。分别通过胸腺嘧啶核苷摄取，细胞周期分析和膜联蛋白V染色测量，该化合物诱导生长抑制，导致具有4N / 8N DNA含量的细胞蓄积，并介导人白血病细胞凋亡。具有野生型p53基因的PALL-1和PALL-2细胞发生了特别深远的生长抑制。相比之下，ZM447439不会抑制从健康正常志愿者那里采集的骨髓定型干细胞的克隆生长。综上所述，抑制Aurora激酶对于白血病患者可能是一种有前途的治疗策略。

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