The flow cytometry-defined light chain cytoplasmic immunoglobulin index and an associated 12-gene expression signature are independent prognostic factors in multiple myeloma.
The flow cytometry-defined light chain cytoplasmic immunoglobulin index and an associated 12-gene expression signature are independent prognostic factors in multiple myeloma.
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DOI：
10.1038/leu.2015.65
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发表时间：
2015-08
期刊：
影响因子：
11.4
通讯作者：
Barlogie B
中科院分区：
文献类型：
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作者：
Papanikolaou X;Alapat D;Rosenthal A;Stein C;Epstein J;Owens R;Yaccoby S;Johnson S;Bailey C;Heuck C;Tian E;Joiner A;van Rhee F;Khan R;Zangari M;Jethava Y;Waheed S;Davies F;Morgan G;Barlogie B
作为全面治疗(TT)3b的一部分，基线骨髓抽吸物接受了核DNA含量和胞浆免疫球蛋白(DNA/CIG)的双色流式细胞术以及血浆细胞基因表达谱(GEP)的检测。检测DNA/CIG衍生参数、GEP和标准临床变量对总生存期(OS)和无进展生存期(PFS)的影响。在DNA/CIG参数中，轻链限制性(LCR)细胞的百分比及其胞浆免疫球蛋白指数(CIG)与不良预后有关。在缺乏GEP资料的情况下，低CIG；2.8、白蛋白3.5 g/dl和年龄⩾6 5岁与较差的OS和PFS显著相关。当包含GEP信息时，低CIG与GEP70定义的高风险和低白蛋白一起存活在模型中。低CIG与β2-微球蛋白5.5 /L、LCR细胞百分率超过50%、C反应蛋白⩾8 mg/L和GEP来源的高中心体指数有关。进一步分析发现，低CIG与细胞周期调节、分化和药物转运有关的12个基因探针之间存在关联，由此得出了TT3b的风险评分，该评分在TT3a、TT2和HOVON试验中也具有预后意义，从而验证了其普遍适用性。低CIG是一个强大的新的预后变量，并已确定了潜在的药物靶点。
As part of Total Therapy (TT) 3b, baseline marrow aspirates were subjected to two-color flow cytometry of nuclear DNA content and cytoplasmic immunoglobulin (DNA/CIG) as well as plasma cell gene expression profiling (GEP). DNA/CIG-derived parameters, GEP and standard clinical variables were examined for their effects on overall survival (OS) and progression-free survival (PFS). Among DNA/CIG parameters, the percentage of the light chain-restricted (LCR) cells and their cytoplasmic immunoglobulin index (CIg) were linked to poor outcome. In the absence of GEP data, low CIg <2.8, albumin <3.5 g/dl and age ⩾65 years were significantly associated with inferior OS and PFS. When GEP information was included, low CIg survived the model along with GEP70-defined high risk and low albumin. Low CIg was linked to beta-2-microglobulin >5.5 mg/l, a percentage of LCR cells exceeding 50%, C-reactive protein ⩾8 mg/l and GEP-derived high centrosome index. Further analysis revealed an association of low CIg with 12 gene probes implicated in cell cycle regulation, differentiation and drug transportation from which a risk score was developed in TT3b that held prognostic significance also in TT3a, TT2 and HOVON trials, thus validating its general applicability. Low CIg is a powerful new prognostic variable and has identified potentially drug-able targets.