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初诊CD38阳性慢性淋巴细胞白血病患者外周血单个核细胞上的趋化因子受体CCR1和CCR2

Chemokine Receptors CCR1 and CCR2 on Peripheral Blood Mononuclear Cells of Newly Diagnosed Patients with the CD38-Positive Chronic Lymphocytic Leukemia.

作者信息

Kholodnyuk Irina, Rivkina Alla, Hippe Laura, Svirskis Simons, Kozireva Svetlana, Ventina Ildze, Spaka Irina, Soloveichika Marina, Pavlova Jelena, Murovska Modra, Lejniece Sandra

机构信息

Institute of Microbiology and Virology, Riga Stradins University, Riga LV-1067, Latvia.

Department of Internal Diseases, Riga Stradins University, Riga LV-1038, Latvia.

出版信息

J Clin Med. 2020 Jul 21;9(7):2312. doi: 10.3390/jcm9072312.

Abstract

Chemokines and their receptors direct migration and infiltration of immune cells. CCR1 and CCR2 maintain sequence similarity and respond to a number of the same chemokines secreted in lymphoid organs. Expression of CD38 on leukemic cells has been associated with poor clinical outcomes in patients with chronic lymphocytic leukemia (CLL) and is considered as the negative predictor of progression. In our study of newly diagnosed CLL patients, which included 39 CD38-positive and 22 CD38-negative patients, CCR1 and/or CCR2 were always detected, using flow cytometry, on the peripheral blood (PB) CD19CD5 lymphocytes in patients with >30% of the CD38 CD19CD5 lymphocytes ( = 16). Spearman's rank correlation analysis determined correlations between the frequency of the CCR1- and CCR2-expressing PB CD19CD5 lymphocytes and the frequency of the CD38-positive CD19CD5 lymphocytes (r = 0.50 and r = 0.38, respectively). No significant correlations were observed between mRNA expression levels in PB mononuclear cells and the frequency of the circulating CCR1 or CCR2 CD19CD5 lymphocytes. Further association studies are needed to verify prognostic relevance of the CCR1/CCR2 expression on leukemic cells in CLL patients at diagnosis. We suggest that CCR1/CCR2 signaling pathways could represent attractive targets for development of CLL anti-progression therapeutics.

摘要

趋化因子及其受体引导免疫细胞的迁移和浸润。CCR1和CCR2保持序列相似性,并对淋巴器官中分泌的许多相同趋化因子产生反应。白血病细胞上CD38的表达与慢性淋巴细胞白血病(CLL)患者的不良临床结果相关,并被视为疾病进展的阴性预测指标。在我们对新诊断的CLL患者的研究中,包括39例CD38阳性和22例CD38阴性患者,使用流式细胞术,在CD38⁺CD19⁺CD5⁺淋巴细胞比例>30%的患者(n = 16)的外周血(PB)CD19⁺CD5⁺淋巴细胞上总是检测到CCR1和/或CCR2。Spearman等级相关分析确定了表达CCR1和CCR2的PB CD19⁺CD5⁺淋巴细胞频率与CD38阳性CD19⁺CD5⁺淋巴细胞频率之间的相关性(分别为r = 0.50和r = 0.38)。在外周血单个核细胞中的mRNA表达水平与循环CCR1或CCR2⁺CD19⁺CD5⁺淋巴细胞频率之间未观察到显著相关性。需要进一步的关联研究来验证诊断时CLL患者白血病细胞上CCR1/CCR2表达的预后相关性。我们认为CCR1/CCR2信号通路可能是开发CLL抗进展疗法的有吸引力的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f39/7408836/055348c4483b/jcm-09-02312-g001.jpg

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