Gene Expression Profiling Reveals Aberrant T-cell Marker Expression on Tumor Cells of Waldenström's Macroglobulinemia.
Gene Expression Profiling Reveals Aberrant T-cell Marker Expression on Tumor Cells of Waldenström's Macroglobulinemia.
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DOI：
10.1158/1078-0432.ccr-18-1435
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Zhan F
中科院分区：
文献类型：
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作者：
Hao M;Barlogie B;Tricot G;Liu L;Qiu L;Shaughnessy JD Jr;Zhan F
Waldenström巨球蛋白血症（WM）的恶性克隆在浆细胞样分化方面表现出显著的克隆内异质性，表明肿瘤发生和进展的机制复杂性。通过比较B细胞的不同阶段来鉴定WM基因可能提供新的药物靶点。将19例WM患者的CD 19 + B细胞（BC）和CD 138+浆细胞（PC）的基因表达特征与外周血和扁桃体的BC以及健康骨髓（N-PC）和多发性骨髓瘤供体（MM-PC）以及扁桃体（T-PC）的PC的基因表达特征进行比较。流式细胞术和免疫荧光法检测WM肿瘤细胞T细胞标志物的表达。与分化缺陷一致，WM病例的BC和PC均表达异常分化标志物。分别在WM-BC和WM-PC中差异表达的55和46个基因的集合;并且在WM样品中鉴定了40个独特失调的基因。失调的基因包括细胞因子、生长因子受体和以前未涉及WM或其他浆细胞恶液质的癌基因。有趣的是，证实了IL 6和IL 6 R两者的强烈上调。PC的监督聚类分析显示，骨髓来源的WM-PC是MM-PC-like或T-PC-like，但不是N-PC-like。在蛋白质水平上证实了T细胞标志物在WM-BC中的异常表达。我们表明，比较微阵列配置文件允许获得更全面的了解WM的生物学。这里提供的数据对新疗法的开发具有影响，例如靶向WM中的异常T细胞标志物。
That the malignant clone of Waldenström’s macroglobulinemia (WM) demonstrates significant intraclonal heterogeneity with respect to plasmacytoid differentiation indicates the mechanistic complexity of tumorigenesis and progression. Identification of WM genes by comparing different stages of B cells may provide novel druggable targets. The gene expression signatures of CD19+ B cells (BC) and CD138+ plasma cells (PC) from 19 patients with WM were compared to those of BC from peripheral blood and tonsil and to those of PC from the marrow of healthy (N-PC) and multiple myeloma donors (MM-PC), as well as tonsil (T-PC). The flow cytometry and immunofluorescence were used to examine T-cell marker expression on WM tumor cells. Consistent with defective differentiation, both BC and PC from WM cases expressed abnormal differentiation markers. Sets of 55 and 46 genes were differentially expressed in WM-BC and WM-PC, respectively; and 40 genes uniquely dysregulated in WM samples were identified. Dysregulated genes included cytokines, growth factor receptors, and oncogenes not previously implicated in WM or other plasma cell dyscrasias. Interestingly, strong upregulation of both IL6 and IL6R was confirmed. Supervised cluster analysis of PC revealed that marrow-derived WM-PC was either MM-PC-like or T-PC-like, but not N-PC-like. The aberrant expression of T cell markers was confirmed at the protein level in WM-BC. We showed that comparative microarray profiles allowed to gain more comprehensive insights into the biology of WM. The data presented here have implications for the development of novel therapies, such as targeting aberrant T-cell markers in WM.