Bone morphogenetic proteins and receptors are over-expressed in bone-marrow cells of multiple myeloma patients and support myeloma cells by inducing ID genes
Bone morphogenetic proteins and receptors are over-expressed in bone-marrow cells of multiple myeloma patients and support myeloma cells by inducing ID genes
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DOI：
10.1016/j.leukres.2009.10.016
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发表时间：
2010-06-01
影响因子：
2.7
通讯作者：
Marusic, Ana
中科院分区：
文献类型：
--
作者：
Grcevic, Danka;Kusec, Rajko;Marusic, Ana
我们评估骨形成蛋白和相关分子在多发性骨髓瘤（MM）中的表达模式和临床相关性。与对照组（n = 15）相比，MM骨髓样品（n = 32）具有增加的BMP 4、BMP 6、ACVR 1和ACVR 2A，以及减少的NOG表达，其中BMP 6具有最高的灵敏度/特异性。在MM骨髓中，BMPs主要来源于CD 138（+）浆细胞群，BMP 6和ACVR 1的表达与浆细胞百分比相关。使用骨髓瘤细胞系NCI H929和Thiel，我们发现BMP诱导ID 1、ID 2和IL 6，并抑制CDKN 1A和BAX基因表达以及BAX蛋白表达。最后，骨形成蛋白部分保护骨髓瘤细胞从硼替佐米和TRAIL诱导的凋亡。我们的结论是，骨形成蛋白可能参与MM的病理生理学，并作为骨髓瘤细胞的生物标志物。(C)2009爱思唯尔有限公司保留所有权利。
We assessed the expression pattern and clinical relevance of BMPs and related molecules in multiple myeloma (MM). MM bone-marrow samples (n = 32) had increased BMP4, BMP6, ACVR1 and ACVR2A, and decreased NOG expression compared with controls (n = 15), with BMP6 having the highest sensitivity/specificity. Within MM bone-marrow, the source of BMPs was mainly CD138(+) plasma-cell population, and BMP6 and ACVR1 expression correlated with plasma-cell percentage. Using myeloma cell lines NCI H929 and Thiel we showed that BMPs induced ID1, ID2 and IL6, and suppressed CDKN1A and BAX gene expression, and BAX protein expression. Finally, BMPs partially protected myeloma cells from bortezomib- and TRAIL-induced apoptosis. We concluded that BMPs may be involved in MM pathophysiology and serve as myeloma cell biomarkers. (C) 2009 Elsevier Ltd. All rights reserved.