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20单核苷酸多态性与美罗华耐药没有相关性但却是弥漫大B细胞淋巴瘤的易感位点

Single nucleotide polymorphisms of CD20 may not contribute to rituximab resistance but is a diffuse large B-cell lymphoma susceptibility locus

中文摘要英文摘要

【目的】:在B细胞非霍奇金淋巴瘤(Non-Hodgkin lymphoma, NHL)的治疗中,CD20是一个重要的靶点。研究目的在于探讨是否存在某种CD20基因的多态性,与B细胞NHL的发病、预后以及美罗华耐药相关。【方法】:采用DNA测序的方法检测了170例初诊B细胞NHL患者的CD20外显子3-8的基因序列,同时通过免疫组化的手段检测了这些患者CD20的表达强度。【结果】:共发现两个单核苷酸多态性(single nucleotide polymorphism,SNP)位点,分别为:5'非翻译区的rs17155019和外显子4序列中的rs2070770 (ILE72/ILE72)。在弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)的患者中,rs2070770位点上,C/T和T/T基因型的频率明显高于正常对照(P=0.013)。换言之,该位点上T等位基因的携带者DLBCL的发病率远高于C等位基因的携带者 (odds ratio=3.314; 95%可信区间2.295-4.787; P<0.001)。另外,在DLBCL的患者中,相比于rs2070770位点上C等位基因的携带者,T等位基因的携带者更多地表现为血清铁蛋白正常及国际预后评分较低(IPI≤3;P值分别为0.036和0.014) 。然而,这两个SNP位点与DLBCL患者的生存都没有明显的相关性。【结论】:CD20的SNP可能并不是DLBCL患者的预后指标,与美罗华的耐药也没有明确的相关性,但rs2070770位点上T等位基因却是DLBCL发病的易感位点。

he integral membrane protein CD20 has been identified as an important target in the treatment of B-cell non-Hodgkin lymphoma. The purpose of this study was to explore whether there are polymorphisms in CD20 that could be associated with tumorigenesis, prognosis, and rituximab resistance. We sequenced exons 3-8 in 170 patients with de novo B-cell non-Hodgkin lymphoma and detected the expression of CD20 via immunohistochemistry. Clinical and laboratory parameters were compared between the patients with and without polymorphisms using a chi-square test. The Kaplan-Meier method was used to construct survival curves, and results were compared using a log-rank test. We found two SNPs: rs17155019 in the 5' untranslated region and rs2070770 (ILE72/ILE72) in exon 4. The C/T and T/T genotypic frequencies of rs2070770 were significantly higher in patients with diffuse large B-cell lymphoma (DLBCL) than in healthy adults (P=0.013). The risk of DLBCL was significantly higher in T allele carriers of rs2070770 than in C allele carriers (odds ratio=3.314; 95% confidence interval 2.295-4.787; P<0.001). DLBCL patients who were T allele carriers of rs2070770 tended to have normal serum ferritin level and a lower international prognostic index (IPI≤3) than C allele carriers (P=0.036 and 0.014, respectively). However, neither SNP seemed to have a significant impact on survival in patients with DLBCL. SNPs of CD20 might not be a prognostic factor for patients with DLBCL and do not contribute to resistance to rituximab but may be a DLBCL susceptibility locus.

徐卫、张丽娜、李建勇

肿瘤学基础医学临床医学

血液学20单核苷酸多态性美罗华耐药弥漫大B细胞淋巴瘤

hematologyCD20single nucleotide polymorphismrituximab resistancediffuse large B-cell lymphoma

徐卫,张丽娜,李建勇.20单核苷酸多态性与美罗华耐药没有相关性但却是弥漫大B细胞淋巴瘤的易感位点[EB/OL].(2013-03-04)[2025-08-18].http://www.paper.edu.cn/releasepaper/content/201303-52.点此复制

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