102例系统性轻链型淀粉样变性患者骨髓浆细胞遗传学特征

Genetic characteristics of bone marrow plasma cells in 102 patients with systemic light chain amyloidosis

目的:明确系统性轻链型淀粉样变性(简称AL型淀粉样变性)患者骨髓浆细胞分子遗传学特征与临床特征、浆细胞表型的相关性。方法:采用间期荧光原位杂交技术(interphase florescence in situ hybridization,iFISH)检测102例AL型淀粉样变性患者骨髓浆细胞染色体畸变情况,分析遗传学异常与患者临床指标、浆细胞表面不同抗原表达之间的潜在关联。结果:102例患者中iFISH检测存在染色体异常有68例(66.67%),其中t(11;14) 35例(51.47%)、1q21扩增22例(32.35%),RB1缺失19例(27.94%),D13S319缺失20例(29.41%), P53缺失4例(5.88%)。存在iFISH异常的患者血清游离轻链差值(difference in involved and uninvolved free light chain,dFLC)显著增高(P=0.001)。存在RB1缺失和D13S319缺失的患者相较其他存在2种染色体异常的患者血清dFLC更高(P=0.022)。CD19阴性组与CD19阳性组相比,iFISH异常比例明显较高(73.53%vs 50%,P=0.026)。结论:AL型淀粉样变性患者骨髓浆细胞遗传学异常检出率为66.67%,其中以t(11;14)最常见。浆细胞遗传学异常与dFLC更高相关;CD19阴性的浆细胞其遗传学异常发生率较CD19阳性的浆细胞更高。

Objective:To identify the molecular genetic characteristics of bone marrow plasma cells in patients with systemic light chain amyloidosis,and explore the correlation between abnormal cytogenetics and clinical characteristics and as well as that between abnormal cytogenetics and plasma cell phenotype.Methodology:Interphase florescence in situ hybridization(iFISH)was used to detect chromosomal aberrations in bone marrow plasma cells of 102 patients with AL amyloidosis,analyzing the potential associations between clinical indicators,immunophenotype of plasma cells and iFISH results.Results:There were 68 of 102(66.67%)patients with AL amyloidosis identified chromosomal abnormalities by iFISH detection,including 35 cases(51.47%)of t(11;14),22 cases(32.35%)of lq21 amplification,20 cases(29.41%)of D13S319 deletion,19 cases(27.94%)with RBI deletion and 4 cases(5.88%)with p53 deletion.And the difference in involved and uninvolved free light chain(dFLC)was significantly higher in patients with abnormal iFISH(P=0.001).Patients with both RBI deletion and D13S319 deletion had higher dFLC than patients with other two types of chromosomal changes(P=0.022).Patients with abnormal iFISH were compared according to the expression of CD19,CD56,and CD117.The proportion of chromosomal abnormalities was significantly higher in the CD 19-negative group than in the CD 19-positive group(73.53%vs 50.00%,P=0.026).Conclusion:The detection rate of genetic abnormality of bone marrow plasma cells in patients with AL amyloidosis is 66.67%,of which t(11;14)is the most common finding.Plasma cytogenetic abnormalities are associated with higher dFLC.CD 19-negative PCs have a higher incidence of genetic abnormalities than CD 19-positive PCs.