多发性骨髓瘤的改良细胞遗传学分析

A modified cytogenetic study for multiple myeloma

目的探讨改进培养方法对多发性骨髓瘤异常核型检出率的影响及染色体异常的临床意义。方法以20例随访诊治的多发性骨髓瘤患者为研究对象，抽取并分离骨髓单个核细胞，分别做直接法、3天培养、以及培养基中添加IL-6（10ng／mL）＋GM-CSF（30ng／mL）的6天培养法后再行R显带分析，以8例缺铁性贫血患者为对照。结果2例多发性骨髓瘤患者标本因凝血试验失败，2例因细胞较少仅行直接法分析，可评估的16例中有4例检出异常核型，其中3例为复杂核型。这些异常核型均见于细胞因子6天处理组，而直接法和3天培养法均未发现异常核型。临床资料显示伴有异常核型的患者疗效均较差、疾病分期都是Ⅲ期，骨髓中瘤细胞比例较高（25％～56％）。对照组病例在各处理组中均未检出异常核型。结论添加细胞因子和延长培养时间有助于提高多发性骨髓瘤异常核型的检出率；多发性骨髓瘤的遗传学改变多为复杂异常，并提示对治疗反应欠佳。

Objective To evaluate the effect of modified culture method used to cytogenetic analysis and the clinically significance of chromosomal abnormalities to multiple myeloma （MM）. Methods Mononuclear cells were isolated from bone marrow aspirate of 20 MM patients ; and then cultured for 3 days without any cytokines, and 6 days in the presence of IL-6 （10 ng/mL） and GM-CSF （30 ng/mL） before RHG banding analysis; the remained part of aspirates were treated directly. Eight cases of iron deficiency anemia were taken as control. Results The experiment was failure in 2 cases because of blood clot, and another 2 cases could be analyzed only by direct method due to inadequate cells. The karyotype abnormalities were found from 4 cases of 16 available patients. Of them, three cases had complex karyotypes. The abnormalities were detected after 6 days culture with addition of cytokines. No abnormalities were detected from those groups of directly analysis and 3 day culture. Meantime, the clinical data showed that the patients with cytoge- netic abnormalities were in stage HI ,and had a high percentage of MM cells （25%-56%） in their bone marrow, and also poor responses to prior chemotherapy. No cytogenetic abnormalities were found from control individuals in all groups. Conclusion Extended culture in the presence of cytokines could improve the efficiency of cytogenetic analysis to MM. Complex karyotype was common cytogenetic abnormalities in MM patients with poor response to chemotherapy.