Waldenstrom巨球蛋白血症的形态学、细胞免疫表型、细胞遗传学以及分子生物学研究

Morphology, immunophenotypes, cytogenetics and molecular biology of Waldenstrom macroglobulinemia

目的分析Waldenstrom巨球蛋白血症（WM）形态学、细胞免疫表型、细胞遗传学以及分子生物学（MICM）异常的特点。方法收集1999至2010年MICM资料完整的初治WM患者41例，男27例、女14例。回顾性分析其临床表现、骨髓形态、细胞免疫表型、细胞遗传学、免疫球蛋白重链基因重排、黑色素瘤优先表达抗原（PRAME）的表达及其与临床预后之间的关系。结果本组中高危患者占58.5%。细胞免疫表型分析：CD19阳性100.0%，CD20阳性97.6%，CD38阳性74.1%，FMC7阳性36.9%，CD5阳性10.0%，CD23阳性31.6%，HLA-DR阳性83.3%，CXCR4阳性85.7%。常规细胞遗传学以及荧光原位杂交发现特异性细胞遗传学异常。PRAME在WM中表达增加，且与骨髓中淋巴细胞数相关， MAGEC1/CT7在WM中不表达。WM使用含利妥昔单抗联合化疗较环磷酰胺＋长春地辛＋醋酸泼尼松（COP）方案治疗未见生存优势。结论 WM具有独特的MICM特征，通过MICM的综合检测有助于早期诊断WM并对疾病进行监测，利妥昔单抗治疗未见明显优势。

Objective To analyze the morphology, immunophenotypes, cytogenetics and molecular biology （MICM） abnomaities of Waldenstrom macroglobulinemia （WM）. Methods Clinical data of 41 patients with newly diagnosed WM from 1999 to 2010 were collected and studied retrospectively （including 27 males and 14 females）. Their clinical manifestations, cell morphology in bone marrow, immunophenotypes, and cytogenetics, immunoglobulin heavy chain gene rearrangement, and expression of preferentially expressed antigen of melanoma （PRAME） were examined by G-banding and FISH, PCR-IgH and RQ-PCR-PRAME and MAGE C1/CT7, and the results were analyzed with clinical prognosis. Results The incidence of high risk patients accounted for 58.5%. Their imunnophenotypes was 100.0%positive to CD19, 97.6%positive to CD20, 74.1%positive to CD38, 36.9%positive to FMC7, 10.0% positive to CD5, 31.6%positive to CD23, 83.3%positive to HLA-DR, and 85.7%positive to CXCR4. There were specific cytogenetic abnormalities found by G-Banding and FISH. RQ-PCR-PRAME had high quantities in WM, which was related to the number of lymphocyte in bone marrow. The MAGE C1/CT7 was negatively expressed in WM. There was no significant survival difference between the Rituximab containing regimen and COP （cyclophosphamide combined with vindisine and prednisone） in treatment of WM. Conclusion WM has specific MICM characteristics. Integrating those measures is helpful to diagnose WM as early as possible, and to monitor the disease during the treatment. Rituximab has no survival benefit in this cohort of patients.