文章：

急性髓系白血病不同遗传亚群中G蛋白偶联受体的转录组分析：潜在疾病特异性靶点的鉴定

Transcriptome analysis of G protein-coupled receptors in distinct genetic subgroups of acute myeloid leukemia: identification of potential disease-specific targets

原文发布日期：2016-06-03

DOI: 10.1038/bcj.2016.36

类型: Original Article

开放获取: 是

英文摘要：

Acute myeloid leukemia (AML) is associated with poor clinical outcome and the development of more effective therapies is urgently needed. G protein-coupled receptors (GPCRs) represent attractive therapeutic targets, accounting for approximately 30% of all targets of marketed drugs. Using next-generation sequencing, we studied the expression of 772 GPCRs in 148 genetically diverse AML specimens, normal blood and bone marrow cell populations as well as cord blood-derived CD34-positive cells. Among these receptors, 30 are overexpressed and 19 are downregulated in AML samples compared with normal CD34-positive cells. Upregulated GPCRs are enriched in chemokine (CCR1, CXCR4, CCR2, CX3CR1, CCR7 and CCRL2), adhesion (CD97, EMR1, EMR2 and GPR114) and purine (including P2RY2 and P2RY13) receptor subfamilies. The downregulated receptors include adhesion GPCRs, such as LPHN1, GPR125, GPR56, CELSR3 and GPR126, protease-activated receptors (F2R and F2RL1) and the Frizzled family receptors SMO and FZD6. Interestingly, specific deregulation was observed in genetically distinct subgroups of AML, thereby identifying different potential therapeutic targets in these frequent AML subgroups.

摘要翻译： 

急性髓系白血病（AML）临床预后较差，亟需开发更有效的治疗方法。G蛋白偶联受体（GPCRs）作为颇具吸引力的治疗靶点，约占已上市药物靶标的30%。通过下一代测序技术，我们研究了148个遗传多样性AML样本、正常血液与骨髓细胞群体以及脐带血来源的CD34阳性细胞中772个GPCR的表达情况。与正常CD34阳性细胞相比，AML样本中有30个受体表达上调，19个受体表达下调。上调的GPCR主要集中在趋化因子（CCR1、CXCR4、CCR2、CX3CR1、CCR7和CCRL2）、黏附（CD97、EMR1、EMR2和GPR114）及嘌呤（包括P2RY2和P2RY13）受体亚家族。下调的受体包括黏附GPCR（如LPHN1、GPR125、GPR56、CELSR3和GPR126）、蛋白酶激活受体（F2R和F2RL1）以及Frizzled家族受体SMO和FZD6。值得注意的是，在遗传特征不同的AML亚群中观察到特定的表达失调现象，从而为这些常见AML亚型识别出不同的潜在治疗靶点。

原文链接：

Transcriptome analysis of G protein-coupled receptors in distinct genetic subgroups of acute myeloid leukemia: identification of potential disease-specific targets