Altered expression of Pax-5 gene in human myeloma cells

Altered expression of Pax-5 gene in human myeloma cells
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DOI:
10.1182/blood.v87.10.4311.bloodjournal87104311
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发表时间:
1996-05-15
期刊:
影响因子:
20.3
通讯作者:
Kawano, MM
Kawano, MM
中科院分区:
医学1区
文献类型:
--
作者:
Mahmoud, MS;Huang, NH;Kawano, MM

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最近的浆细胞表型分析表明,正常浆细胞确实表达B细胞谱系特异性分子CD19,但其恶性对应物(骨髓瘤细胞)是CD19(-)。为了阐明骨髓瘤细胞上CD 19抗原缺失的意义,我们首先比较了CD 19和Pax-5基因在B细胞、正常浆细胞、骨髓瘤细胞系和原发性骨髓瘤细胞中的表达,因为据报道Pax-5基因编码CD 19基因表达所必需的转录因子B细胞特异性活化蛋白(BSAP)。在这些原发性骨髓瘤细胞和细胞系中均未检测到CD 19和Pax-5 mRNA,而正常浆细胞表达CD 19和Pax-5 mRNA。此外,我们可以证实,BSAP结合活性中未检测到的核提取物从CD19(-)骨髓瘤细胞系(KMS-5),但检测到的CD19(+)B细胞系(Raji)的凝胶迁移试验。我们进一步检测了E2A和Id基因的表达,因为E2A和Id分别被认为是Pax-5基因表达的正调控因子和负调控因子。然而,这些E2A和Id-2基因的表达没有显着差异,可以观察到骨髓瘤细胞和正常浆细胞之间。因此,这些数据表明,Pax-5的表达改变,而不是E2A或Id,是负责人骨髓瘤细胞中的CD19表达的损失,虽然Pax-5基因表达改变的潜在机制仍有待澄清。(C)1996年,美国血液学会。
Recent phenotypic analysis of plasma cells showed that normal plasma cells do express the B-cell lineage-specific molecule CD19, but their malignant counterpart (myeloma cells) are CD19(-). To clarify the meaning of loss of CD19 antigen on myeloma cells, we first compared the expression of CD19 and Pax-5 genes among B cells, normal plasma cells, myeloma cell lines, and primary myeloma cells, because the Pax-5 gene was reported to encode the transcriptional factor, B-cell-specific activating protein (BSAP), necessary for CD19 gene expression. Neither CD19 nor Pax-5 mRNA could be detected in those primary myeloma cells and cell lines, whereas normal plasma cells did express both CD19 and Pax-5 mRNA. Furthermore, we could confirm that BSAP-binding activity was not detected in the nuclear extract from CD19(-) myeloma cell line (KMS-5) but was detected in CD19(+) B-cell line (Raji) by gel-shift assay. We further examined the expression of E2A and Id genes, because E2A and Id are considered to be positive and negative regulators in the expression of Pax-5 gene, respectively. However, no significant differences in the expression of these E2A and Id-2 genes could be observed between myeloma cells and normal plasma cells. Therefore, these data suggest that the altered expression of Pax-5, but not E2A or Id, is responsible for the loss of CD19 expression in human myeloma cells, although the underlying mechanism of the altered Pax-5 gene expression remains to be clarified. (C) 1996 by The American Society of Hematology.