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蛋白激酶的基因表达谱揭示了慢性淋巴细胞白血病的独特特征,并且体外实验支持第二代蛋白激酶抑制剂的作用。

Gene expression profile of protein kinases reveals a distinctive signature in chronic lymphocytic leukemia and in vitro experiments support a role of second generation protein kinase inhibitors.

机构信息

Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Via Benevento, Rome, Italy.

出版信息

Leuk Res. 2010 Jun;34(6):733-41. doi: 10.1016/j.leukres.2009.11.005. Epub 2009 Dec 24.

Abstract

To investigate the role of protein kinases (PKs) in chronic lymphocytic leukemia (CLL), we performed gene expression profile on 505 PK genes. Comparison between CLL with acute lymphocytic leukemia (ALL) patients highlighted an homogeneous up-modulation of several PKs in CLL, 16 also overexpressed in two additional CLL cohorts. Q-PCR analysis confirmed these findings. No differences were observed in the main prognostic subclasses, indicating that PK overexpression is specific of the disease itself. Tests in vitro showed that Dasatinib partially reduced CLL cells viability, mostly in IGHV germline patients. These findings suggest that treatment with second generation tyrosine kinase (TK) inhibitors may represent an attractive therapeutic strategy for CLL patients.

摘要

为了探究蛋白激酶(PKs)在慢性淋巴细胞白血病(CLL)中的作用,我们对 505 个 PK 基因进行了基因表达谱分析。将 CLL 患者与急性淋巴细胞白血病(ALL)患者进行比较,结果显示 CLL 中多种 PK 呈均匀上调,其中 16 种在另外两个 CLL 队列中也过表达。Q-PCR 分析证实了这些发现。在主要的预后亚类中没有观察到差异,这表明 PK 过表达是疾病本身所特有的。体外试验表明,Dasatinib 可部分降低 CLL 细胞的活力,主要在 IGHV 胚系患者中。这些发现表明,使用第二代酪氨酸激酶(TK)抑制剂治疗可能是 CLL 患者的一种有吸引力的治疗策略。

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