在多发性骨髓瘤的非移植患者中，克隆型细胞的预处理水平可预测无事件生存。
In non-transplant patients with multiple myeloma, the pre-treatment level of clonotypic cells predicts event-free survival.
机构信息
Department of Oncology, University of Alberta and Cross Cancer Institute, 11560 University Avenue, Edmonton, AB, T6G1Z2, Canada.
出版信息
Mol Cancer. 2012 Oct 19;11:78. doi: 10.1186/1476-4598-11-78.
BACKGROUND
In multiple myeloma (MM), the immunoglobulin heavy chain VDJ gene rearrangement is a unique clonotypic signature that identifies all members of the myeloma clone independent of morphology or phenotype. Each clonotypic MM cell has only one genomic copy of the rearranged IgH VDJ.
METHODS
Pre-treatment bone marrow aspirates from myeloma patients at diagnosis or in relapse were evaluated for the number of clonotypic cells using real time quantitative PCR (RPCR). RPCR measured the level of clonal cells, termed VDJ%, in 139 diagnosis and relapse BM aspirates from MM patients.
RESULTS
Patients with a VDJ% below the median had a significantly longer event free survival (EFS) then those with a VDJ% higher than the median (p=0.0077, HR=0.57). Further, although the VDJ% from non-transplant patients predicted EFS (p=0.0093), VDJ% failed to predict outcome after autologous stem cell transplant (p=0.53).
CONCLUSIONS
Our results suggest that for non-transplant patients, the tumor burden before treatment, perhaps reflecting cancer stem cell progeny/output, is an indirect measure that may indicate the number of MM cancer stem cells and hence event free survival.
背景
在多发性骨髓瘤（MM）中，免疫球蛋白重链 VDJ 基因重排在形态学或表型上独立识别骨髓瘤克隆的所有成员，是独特的克隆型特征。每个克隆型骨髓瘤细胞仅有一个重排的 IgH VDJ 的基因组拷贝。
方法
使用实时定量 PCR（RPCR）检测诊断或复发时骨髓瘤患者的骨髓抽吸物中克隆性细胞的数量。RPCR 测量了来自 139 例 MM 患者的诊断和复发 BM 抽吸物中克隆细胞的水平，称为 VDJ%。
结果
VDJ%低于中位数的患者的无事件生存（EFS）显著长于 VDJ%高于中位数的患者（p=0.0077，HR=0.57）。此外，尽管非移植患者的 VDJ%预测 EFS（p=0.0093），但 VDJ%未能预测自体干细胞移植后的结果（p=0.53）。
结论
我们的结果表明，对于非移植患者，治疗前的肿瘤负担，可能反映了癌症干细胞的后代/输出，是一个间接的衡量标准，可能表明 MM 癌症干细胞的数量，从而表明无事件生存。
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