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探索血液系统癌症中的G蛋白偶联受体

Exploring G Protein-Coupled Receptors in Hematological Cancers.

作者信息

Tsang Choi Har, Kozielewicz Pawel

机构信息

Molecular Pharmacology of GPCRs, Department Physiology & Pharmacology, Karolinska Institutet, Biomedicum, 171 65 Stockholm, Sweden.

出版信息

ACS Pharmacol Transl Sci. 2024 Nov 21;7(12):4000-4009. doi: 10.1021/acsptsci.4c00473. eCollection 2024 Dec 13.

Abstract

Hematological cancers, such as lymphomas and leukemias, pose significant challenges in oncology, necessitating a deeper understanding of their molecular landscape to enhance therapeutic strategies. This article critically examines and discusses recent research on the roles of G protein-coupled receptors (GPCRs) in myeloma, lymphomas, and leukemias with a particular focus on pediatric acute lymphoblastic (lymphocytic) leukemia (ALL). By utilizing RNA sequencing (RNA-seq), we analyzed GPCR expression patterns in pediatric ALL samples (aged 3-12 years old), with a further focus on Class A orphan GPCRs. Our analysis revealed distinct GPCR expression profiles in pediatric ALL, identifying several candidates with aberrant upregulated expression compared with healthy counterparts. Among these GPCRs, GPR85, GPR65, and GPR183 have varying numbers of studies in the field of hematological cancers and pediatric ALL. Furthermore, we explored missense mutations of pediatric ALL in relation to the RNA gene expression findings, providing insights into the genetic underpinnings of this disease. By integrating both RNA-seq and missense mutation data, this article aims to provide an insightful and broader perspective on the potential correlations between specific GPCR and their roles in pediatric ALL.

摘要

血液系统癌症,如淋巴瘤和白血病,给肿瘤学带来了重大挑战,因此有必要更深入地了解其分子格局,以改进治疗策略。本文批判性地审视和讨论了关于G蛋白偶联受体(GPCR)在骨髓瘤、淋巴瘤和白血病中作用的最新研究,特别关注儿童急性淋巴细胞(淋巴细胞)白血病(ALL)。通过利用RNA测序(RNA-seq),我们分析了儿童ALL样本(3至12岁)中的GPCR表达模式,进一步聚焦于A类孤儿GPCR。我们的分析揭示了儿童ALL中不同的GPCR表达谱,确定了与健康对照相比有异常上调表达的几个候选者。在这些GPCR中,GPR85、GPR65和GPR183在血液系统癌症和儿童ALL领域有不同数量的研究。此外,我们探讨了与RNA基因表达结果相关的儿童ALL错义突变,为该疾病的遗传基础提供了见解。通过整合RNA-seq和错义突变数据,本文旨在就特定GPCR与其在儿童ALL中的作用之间的潜在关联提供有见地且更广泛的观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb36/11651347/53963a99af7d/pt4c00473_0001.jpg

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