非霍奇金淋巴瘤BCL-XL基因表达及突变的研究_医学论文.docVIP

非霍奇金淋巴瘤BCL-XL基因表达及突变的研究_医学论文 非霍奇金淋巴瘤BCL-XL基因表达及突变的研究_医学论文 作者：刘元华, Christophe Leboeuf, 金晓龙,肖家诚, Anne Janin, 陈赛娟，赵维莅【摘要】 本研究探讨78例非霍奇金淋巴瘤BCL-XL表达和突变的发生率及其临床意义。应用激光微切割技术从淋巴结组织中特异地分离淋巴瘤细胞，用实时定量RT-PCR法检测淋巴瘤组织和淋巴瘤细胞中BCL-XL的表达，PCR直接测序法检测BCL-XL的突变情况。结果表明：与淋巴结反应性增生（15例）相比，滤泡性淋巴瘤（30例）组织和微切割的淋巴瘤细胞均高表达BCL-XL（P值分别为0.0064和lt0.0001），而T细胞淋巴瘤（24例）和弥漫性大B细胞淋巴瘤（24例）中BCL-XL表达无明显升高。在滤泡性淋巴瘤中，BCL-XL高表达的患者常伴多个淋巴结外器官累及（P=0.0004），血清乳酸脱氢酶水平升高（P=0.0019），国际预后指数分组多为高危组（P=0.0013），患者总生存期短（P=0.0451）。突变检测发现1例滤泡性淋巴瘤BCL-XL的同义突变（密码子 109 ACA→ACC）。结论：BCL-XL表达与滤泡性淋巴瘤的疾病进展和患者预后密切相关。 【关键词】 非霍奇金淋巴瘤；BCL-XL基因；基因表达；基因突变 　　BCL-XL Expression and Mutation in Non-Hodgkin′s Lymphoma AbstractThe study was aimed to investigate the BCL-XL expression and mutation, and its clinical significance in non-Hodgkin′s lymphoma. Lymphoma cells were selectively isolated by laser microdissection. BCL-XL expression from lymphoma tissue and microdissected lymphoma cells was measured by using real-time quantitative reverse transcription-polymerase chain reaction. BCL-XL mutation was analyzed by using direct sequencing of PCR products. The results showed that compared to 15 patients with reactive hyperplasia, BCL-XL was overexpressed in follicular lymphoma (n=30), both in lymphoma tissue (P=0.0064) and in microdissected lymphoma cells (0.0001). No significant rise of BCL-XL expression was observed in patients with T-cell lymphoma (n=24) and diffuse large B cell lymphoma (n=24). In follicular lymphoma, high BCL-XL level was associated with multiple extranodal involvement (P=0.0004), elevated lactate dehydrogenase level (P=0.0019), high-risk international prognostic index (P=0.0013) and a short overall survival time (P=0.0451). Mutation analysis revealed one synonymous mutation (Codon 109 ACA→ACC) in one case of follicular lymphoma patient. It is concluded that BCL-XL expression is closely correlated with progress of follicular lymphoma and prognosis of patients with follicular lymphoma. The value of BCL-XL expression as a prognostic mar