B细胞恶性肿瘤患者血浆游离DNA中IgH基因重排检测及临床意义  

Clinical application of detecting immunoglobulin heavy chain rearrangement in plasma DNA of patients with B-cell malignancies

作　　者：李洁[1] 徐兵[1] 宋小燕[1] 陈国枢[1] 周淑芸[1] 

机构地区：[1]南方医科大学南方医院血液科,广州510515

出　　处：《广东医学》2008年第4期576-578,共3页Guangdong Medical Journal

基　　金：广东省自然科学基金资助项目(编号:5004737);广东省医学科研基金资助项目(编号:A2005391)

摘　　要：目的探讨检测B细胞肿瘤患者血浆DNA标本IgH基因重排对辅助诊断及判断预后的临床意义。方法采集83例B细胞急性淋巴细胞白血病（B-ALL）、B细胞非霍奇金淋巴瘤（B-NHL）及多发性骨髓瘤（MM）患者共110份血浆标本，提取血浆游离DNA，PCR检测IgH基因重排。结果63例初发B细胞肿瘤患者IgH基因重排检测阳性率为77．8％，而缓解病例的阳性率为27．6％，初发患者检测阳性率显著高于缓解病例（P〈0．01）。结缔组织病、感染性疾病及健康人均呈阴性结果。IgH基因重排检测阳性率与B-NHL和MM的分期、血清β2-微球蛋白（β2-Me）和乳酸脱氢酶（LDH）水平无关（P〉0．05）。追踪检测16例患者显示12例初发检测阳性者治疗缓解后转为阴性，其中3例缓解后6-9个月检测血浆IgH基因重排再次转为阳性，随后此3例患者均出现临床复发，检测转阳较临床复发提前1-4个月。1例在初诊和完全缓解期间检测均为阳性ALL患者，经异基因干细胞移植后转为阴性；3例检测始终阳性的患者疗效不佳，始终未获缓解。结论初治B细胞肿瘤患者血浆游离DNA中检测IgH基因重排阳性率高、特异性强、取材简便，有望用于B细胞肿瘤辅助诊断，追踪检测还有助于判断预后。Objective To evaluate the significance of detecting immunoglobulin heavy chain （ IgH ） gene rear-rangement in plasma DNA of patients with B - cell malignancies. Methods DNA was extracted from plasma samples col- lected from 83 patients with B - acute lymphoblastic leukemia （ B - ALL）, B non - hodgkin＇s lymphoma （ B - NHL） and multiple myeloma （MM） patients, IgH gene rearrangement was detected by polymerase chain reaction （PCR） amplification. Results 77.8% patients with de novo B -cell malignancies were found with IgH gene rearrangement in plasma DNA sample. Among B - cell malignancies in complete remission （ CR）, only 27.6% of plasma DNA samples were detec- ted with IgH gene rearrangement, which was significantly lower than that of de novo patients（P 〈0. 01 ）. IgH gene rear- rangement were not detected in Plasma samples with connective tissue disease, infectious patients and healthy donors. There was no statistical correlation between IgH gene rearrangement and clinical staging, β2-microglobulin（β2-MG） levels or lactic dehydrogenase （LDH） levels. Follow - up studies showed a close correlation of IgH gene rearrangement with disease states. Twelve patients turned PCR negative in plasma when they reached clinical CR after chemotherapy hut turned positive 6 to 9 months later. These 3 cases all suffered clinical relapse later. IgH gene rearrangement turned posi- tive 1 to 4 months before the relapse. One patient who had positive results in diagnosis and CR turned PCR negative after allogeneic hematopoietic stem cell transplantation. Three patients who were repeatedly positive for IgH rearrangement showed refractory response and a poor prognosis. Conclusion IgH gene rearrangement can be detected in plasma DNA in newly diagnosed patients with B -cell malignancies and has high positive rate and specificity. It can be used as a useful parameter for development of noninvasive diagnostic, prognostic and follow - up tests for malignancies.

关 键 词：B细胞 肿瘤 血浆 DNA 免疫球蛋白 重链 基因重排 PCR 

分 类 号：R733.71[医药卫生—肿瘤] R734.202[医药卫生—临床医学]