Fc receptor-like 1-5 molecules are similarly expressed in progressive and indolent clinical subtypes of B-cell chronic lymphocytic leukemia

Fc receptor-like 1-5 molecules are similarly expressed in progressive and indolent clinical subtypes of B-cell chronic lymphocytic leukemia
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DOI:
10.1002/ijc.23751
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发表时间:
2008-11-01
影响因子:
6.4
通讯作者:
Shokri, Fazel
Shokri, Fazel
中科院分区:
医学1区
文献类型:
--
作者:
Kazemi, Tohid;Asgarian-Omran, Hossein;Shokri, Fazel

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Fc受体样(FCRL)1-5分子仅在B细胞中表达,最近被认为是B细胞恶性肿瘤免疫治疗的潜在靶点。在这项研究中,FCRL 1 -5分子的表达模式进行了研究,在伊朗B细胞慢性淋巴细胞白血病(B-CLL)患者。我们的RT-PCR结果表明,所有的FCRL分子,除了FCRL 4,表达在绝大多数的B-CLL患者。然而,在B-CLL(n = 86)和老年正常受试者(n = 10)之间FCRL的相对mRNA表达水平的比较显示,在B-CLL病例中,FCRL 1(p < 0.0001)、FCRL 3(p = 0.01)和FCRL 4(p = 0.002)的表达水平显著较低,但FCRL 2或FCRL 5的表达水平不低。在B-CLL患者的惰性和进行性亚型之间没有观察到显著差异。突变和灭活亚型之间的比较揭示了突变CLL患者中FCRL 3的表达水平显著更高(p = 0.017)。流式细胞术检测12例白血病细胞表面和胞浆内FCRL 1、2、4和5的表达,除少数例外,结果与RT-PCR相似。因此,虽然FCRL 4仅在2个样品中在胞质内水平表达,但FCRL 1和2在大多数样品中在表面和胞质内表达。在10个样本中也检测到FCRL 5蛋白,但仅在2个样本中确认了表面表达。通过流式细胞术对来自5名正常受试者的B细胞的分析显示,与CLL相比,FCRL分子的表达水平更高。我们的研究结果表明FCRL分子在B-CLL中的差异表达,并提示FCRL 1和2对免疫干预的潜在意义。(c)2008 Wiley-Liss,Inc.
Fc receptor-like (FCRL) 1-5 molecules are exclusively expressed in B-cells and have recently been considered as potential targets for immunotherapy of B-cell malignancies. In this study, the expression pattern of FCRL1-5 molecules was investigated in Iranian patients with B-cell chronic lymphocytic leukemia (B-CLL). Our RT-PCR results have demonstrated that all FCRL molecules, except FCRL4, were expressed in the vast majority of the patients with B-CLL. However, comparison of the relative mRNA expression levels of FCRL between B-CLL (n = 86) and elderly normal subjects (n = 10) revealed significantly lower expression levels of FCRL1 (p < 0.0001), FCRL3 (p = 0.01) and FCRL4 (p = 0.002), but not FCRL2 or FCRL5, in cases with B-CLL. No significant differences were observed between the indolent and progressive subtypes of patients with B-CLL. Comparison between the mutated and immolated subtypes revealed a significantly higher expression level of FCRL3 (p = 0.017) in patients with mutated CLL. Surface and intracytoplasmic expression of FCRL1, 2, 4 and 5 in leukemic cells of 12 patients by flow cytometry revealed similar results to those obtained by RT-PCR with a few exceptions. Thus, while FCRL4 was expressed in only 2 samples at intracytoplasmic level, FCRL1 and 2 were expressed in the majority of samples, both at surface and intracytoplasm. FCRL5 protein was also detected in 10 samples, but surface expression was confirmed in only 2. Analysis of B-cells from 5 normal subjects by flow cytometry revealed higher expression levels of FCRL molecules compared to CLL. Our results indicate differential expression of FCRL molecules in B-CLL and suggest the potential implication of FCRL1 and 2 for immunotherapeutic interventions. (c) 2008 Wiley-Liss, Inc.