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巨噬细胞炎性蛋白1α(MIP-1α)可能与结外NK/T细胞淋巴瘤患者的不良预后相关。

Macrophage inflammatory protein 1 alpha (MIP-1α) may be associated with poor outcome in patients with extranodal NK/T-cell lymphoma.

作者信息

Kim Hae Su, Ryu Kyung Ju, Ko Young Hyeh, Kim Hee-Jin, Kim Sun-Hee, Kim Won Seog, Kim Seok Jin

机构信息

Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Korea.

Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.

出版信息

Hematol Oncol. 2017 Sep;35(3):310-316. doi: 10.1002/hon.2283. Epub 2016 Feb 29.

DOI:10.1002/hon.2283
PMID:26928433
Abstract

The macrophage inflammatory protein 1α (MIP-1α) is anticipated to have a role in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) because the expression of MIP-1α is related to Epstein-Barr virus (EBV) latency in EBV-related non-Hodgkin lymphoma cells. Thus, we measured the serum level of MIP-1α in 69 patients with ENKTL using frozen serum samples that were archived at diagnosis. As serum level of MIP-1α was not detectable in 19 patients (range: 0-24.37 pg/mL), patients were dichotomized into positive (n = 50) and negative (n = 19) MIP-1α groups according to the presence of detectable level of MIP-1α in serum. MIP-1α-positive group showed a significantly poor overall survival (OS) in comparison with the MIP-1α-negative group (p = 0.004). In the subgroup analysis, the positivity of MIP-1α was significantly associated with OS in patients with stage IIIE/IV and a detectable level of EBV DNA (p = 0.002 and 0.032, respectively). Multivariate analysis also showed that the positivity of MIP-1α was independently associated with worse OS together with bone marrow involvement (p = 0.002). An in vitro study with patient-derived ENKTL tumour cells showed the expression of CCR1 and CCR5 on the surface of tumour cells (28% and 14%, respectively) , and the addition of MIP-1α to the culture media of tumour cells increased cell growth supporting the negative impact of MIP-1α on the prognosis of ENKTL patients. In conclusion, serum levels of MIP-1α could predict survival outcomes in patients with ENKTL. Therefore, MIP-1α should be considered for prognostication and a potential therapeutic target. Copyright © 2016 John Wiley & Sons, Ltd.

摘要

巨噬细胞炎性蛋白1α(MIP-1α)有望在结外自然杀伤(NK)/T细胞淋巴瘤(ENKTL)中发挥作用,因为MIP-1α的表达与EB病毒(EBV)在EBV相关非霍奇金淋巴瘤细胞中的潜伏有关。因此,我们使用诊断时存档的冷冻血清样本,检测了69例ENKTL患者的血清MIP-1α水平。由于19例患者(范围:0 - 24.37 pg/mL)的血清中未检测到MIP-1α水平,根据血清中是否可检测到MIP-1α水平,将患者分为MIP-1α阳性组(n = 50)和阴性组(n = 19)。与MIP-1α阴性组相比,MIP-1α阳性组的总生存期(OS)显著较差(p = 0.004)。在亚组分析中,MIP-1α阳性与ⅢE/Ⅳ期且可检测到EBV DNA水平的患者的OS显著相关(分别为p = 0.002和0.032)。多因素分析还显示,MIP-1α阳性与骨髓受累一起独立地与较差的OS相关(p = 0.002)。一项对患者来源的ENKTL肿瘤细胞的体外研究显示,肿瘤细胞表面CCR1和CCR5的表达(分别为28%和14%),并且在肿瘤细胞培养基中添加MIP-1α可促进细胞生长,这支持了MIP-1α对ENKTL患者预后的负面影响。总之,MIP-1α血清水平可预测ENKTL患者的生存结果。因此,MIP-1α应被考虑用于预后评估和作为潜在的治疗靶点。版权所有© 2016约翰威立父子有限公司

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