The Impact of Clone Size on the Prognostic Value of Chromosome Aberrations by Fluorescence In Situ Hybridization in Multiple Myeloma
The Impact of Clone Size on the Prognostic Value of Chromosome Aberrations by Fluorescence In Situ Hybridization in Multiple Myeloma
复制标题
多发性骨髓瘤荧光原位杂交克隆大小对染色体畸变预后价值的影响。
DOI：
10.1158/1078-0432.ccr-14-2576
复制
发表时间：
2015-05-01
影响因子：
11.5
通讯作者：
Qiu, Lugui
中科院分区：
文献类型：
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作者：
An, Gang;Li, Zengjun;Qiu, Lugui
目的：越来越多的证据表明，肿瘤内异质性在多发性骨髓瘤中普遍存在，并且在骨髓瘤细胞群中存在多个遗传上不同的亚克隆的集合。目前尚不清楚具有独特细胞遗传学异常的克隆性骨髓瘤群体的大小是否具有任何额外的预后价值。实验设计：我们通过荧光原位杂交分析了333例新诊断骨髓瘤患者和92例复发骨髓瘤患者在不同临界值下细胞遗传学畸变对预后的影响。结果如下：我们发现，几乎所有的免疫球蛋白相关的安排中观察到的绝大多数纯化的浆细胞，然而，13 q缺失，17 p缺失，和1 q21扩增出现在恶性浆细胞群体中的不同百分比。根据携带这些细胞遗传学畸变的亚克隆的大小，将患者分为四组：0%-10%、10.5%-20%、20.5%-50%和> 50%。受试者操作特征分析用于确定具有最大生存差异的最佳截止值，并显示最强大的克隆大小为13 q缺失的10%，17 p缺失的50%，1 q21增益的20%，这提供了预测不良结局的最佳截止值。结论：我们的研究表明，克隆大小对预后价值的影响在特定的遗传异常之间存在差异。即使是一个亚组的浆细胞窝藏13 q缺失和1 q21增益的细胞遗传学畸变的预后价值进行了观察，然而，17 p缺失显示最强大的截止预测生存只有当占主导地位的克隆窝藏异常。临床癌症研究; 21（9）; 2148-56。©2015 AACR.
Purpose: Accumulating evidence indicates that intratumor heterogeneity is prevalent in multiple myeloma and that a collection of multiple, genetically distinct subclones are present within the myeloma cell population. It is not clear whether the size of clonal myeloma populations harboring unique cytogenetic abnormalities carry any additional prognostic value. Experimental Design: We analyzed the prognostic impact of cytogenetic aberrations by fluorescence in situ hybridization at different cutoff values in a cohort of 333 patients with newly diagnosed myeloma and 92 patients with relapsed myeloma. Results: We found that nearly all IgH-related arrangements were observed in a large majority of the purified plasma cells; however, 13q deletion, 17p deletion, and 1q21 amplification appeared in different percentages within the malignant plasma cell population. Based on the size of subclones carrying these cytogenetic aberrations, the patients were divided into four groups: 0%–10%, 10.5%–20%, 20.5%–50%, and >50%. Receiver-operating characteristics analysis was applied to determine the optimal cutoff value with the greatest differential survival and showed that the most powerful clone sizes were 10% for 13q deletion, 50% for 17p deletion, and 20% for 1q21 gains, which provided the best possible cutoffs for predicting poor outcomes. Conclusions: Our study indicated that the impact of clone size on prognostic value varies between specific genetic abnormalities. Prognostic value was observed for even a subgroup of plasma cells harboring the cytogenetic aberration of 13q deletion and 1q21 gains; however, 17p deletion displayed the most powerful cutoff for predicting survival only if the predominant clones harbored the abnormality. Clin Cancer Res; 21(9); 2148–56. ©2015 AACR.