Gene expression of anti- and pro-apoptotic proteins in malignant and normal plasma cells
Gene expression of anti- and pro-apoptotic proteins in malignant and normal plasma cells
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DOI：
10.1111/j.1365-2141.2008.07562.x
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发表时间：
2009-04-01
影响因子：
6.5
通讯作者：
Klein, Bernard
中科院分区：
文献类型：
--
作者：
Jourdan, Michel;Reme, Thierry;Klein, Bernard
恶性浆细胞的存活是疾病发生、发展和化疗耐药的关键。使用DNA微阵列，我们分析了与外在和内在凋亡途径，半胱天冬酶和凋亡抑制蛋白的58个蛋白质编码基因的表达。我们对92例初诊患者的记忆B细胞（MBC）、浆母细胞（PPC）、骨髓浆细胞（BMPC）和纯化骨髓瘤细胞（MMC）进行了研究。58个探针组中的40个能够将MBC、PPC和BMPC分离成三个同源簇，其特征在于MBC的TNFRSF10A、TNFRSF10B、BCL 2A1、CASP8、CASP9和PMAIP1基因的表达升高，PPC的FAS、FADD、AIFM1、BIRC 5、CASP、CASP2、CASP3和CASP6的表达升高，以及BMPC的BCL 2、MCL 1、BID、BIRC 3和XIAP的表达升高。因此，B细胞分化与促凋亡和抗凋亡基因表达的变化有关。关于MMC，主要发现是TRAIL上调，其可能被BM基质细胞的高骨保护素产生和与正常BMPC相比FAS、APAF 1和BNIP 3的表达降低所抵消。在40个基因中，CASP2和BIRC 5在MMC中的表达在两个独立的先前未经治疗的患者系列中具有不良预后。
The survival of malignant plasma cells is a key event in disease occurrence, progression and chemoresistance. Using DNA-microarrays, we analysed the expression of genes coding for 58 proteins linked with extrinsic and intrinsic apoptotic pathways, caspases and inhibitor of apoptosis proteins. We considered six memory B cells (MBC), seven plasmablasts (PPC), seven bone marrow plasma cells (BMPC) and purified myeloma cells (MMC) from 92 newly-diagnosed patients. Forty out of the 58 probe sets enabled the separation of MBC, PPC and BMPC in three homogeneous clusters, characterized by an elevated expression of TNFRSF10A, TNFRSF10B, BCL2A1, CASP8, CASP9 and PMAIP1 genes for MBC, of FAS, FADD, AIFM1, BIRC5, CASP CASP2, CASP3 and CASP6 for PPC and of BCL2, MCL1, BID, BIRC3 and XIAP for BMPC. Thus, B cell differentiation was associated with change of expression of pro-apoptotic and anti-apoptotic genes. Regarding MMC, the major finding was TRAIL upregulation that might be counteracted by a high osteoprotegerin production by BM stromal cells and a decreased expression of FAS, APAF1 and BNIP3 compared to normal BMPC. Out of the 40 genes, CASP2 and BIRC5 expression in MMC had adverse prognosis in two independent series of previously-untreated patients.