BCL-X expression in multiple myeloma: possible indicator of chemoresistance.
BCL-X expression in multiple myeloma: possible indicator of chemoresistance.
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发表时间：
1998-01
期刊：
影响因子：
11.2
通讯作者：
Y. Tu;S. Renner;F. Xu;A. Fleishman;J. Taylor;J. Weisz;R. Vescio;M. Rettig;J. Berenson
中科院分区：
文献类型：
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作者：
Y. Tu;S. Renner;F. Xu;A. Fleishman;J. Taylor;J. Weisz;R. Vescio;M. Rettig;J. Berenson
由于小鼠骨髓瘤浆细胞和正常人淋巴结浆细胞表达BCL-X，我们评估了BCL-X在恶性人浆细胞中的表达。在几种人骨髓瘤细胞系以及从一些患者获得的CD 38分选的骨髓细胞中检测到BCL-X表达。仅检测到抗凋亡长型BCL-X（BCL-X-L）。由于BCL-X-L表达可以保护肿瘤细胞免于化疗药物诱导的凋亡，我们在55例存档骨髓活检中检测了表达的临床相关性。活检组织进行免疫组化染色，BCL-X表达与随后的治疗反应相关。在接受美法仑和泼尼松或长春新碱、阿霉素和地塞米松治疗的患者组中，恶性浆细胞中的BCL-X表达与缓解率下降密切相关。非BCL-X表达病例的缓解率为83-87%，BCL-X表达病例的缓解率为20-31%。此外，BCL-X表达在复发患者（77%）的标本中更常见，与初次诊断时（29%）相比。对8226 dox-40细胞系的研究进一步支持了耐药性与BCL-X-L表达的相关性。该细胞系表达p-糖蛋白并作为多发性骨髓瘤细胞中多药耐药的模型，证明了BCL-X-L的上调表达，这是相对特异的，因为BCL-2或BAX表达没有改变。此外，dox-40细胞表现出对由几种不同药剂诱导的凋亡的普遍抗性。这些结果表明，恶性浆细胞可以表达BCL-X-L，并且这种表达可能是化学抗性疾病的标志。
Because murine myeloma plasma cells and normal human lymph node plasma cells express BCL-X, we evaluated BCL-X expression in malignant human plasma cells. BCL-X expression was detected in several human myeloma cell lines, as well as in CD38-sorted bone marrow cells obtained from some patients. Only the antiapoptotic long form of BCL-X (BCL-X-L), was detected. Because BCL-X-L expression can protect tumor cells from apoptotic death induced by chemotherapeutic agents, we tested the clinical relevance of expression in 55 archival bone marrow biopsies. The biopsies were stained by immunohistochemistry, and BCL-X expression was correlated with the subsequent response to treatment. BCL-X expression in malignant plasma cells strongly correlated with decreased response rates in patient groups treated with either melphalan and prednisone or vincristine, Adriamycin, and dexamethasone. Response rates were 83-87% in non-BCL-X-expressing cases and 20-31% in BCL-X-expressing cases. In addition, BCL-X expression was more frequent in specimens taken from patients at relapse (77%), when compared to those at initial diagnosis (29%). Further support for the association of drug resistance with BCL-X-L expression came from studies of the 8226 dox-40 cell line. This line, which expresses p-glycoprotein and serves as a model of multidrug resistance in multiple myeloma cells, demonstrated an up-regulated expression of BCL-X-L, which was relatively specific, in that BCL-2 or BAX expression was not altered. In addition, dox-40 cells demonstrated a generalized resistance to apoptosis that was induced by several different agents. These results indicate that malignant plasma cells can express BCL-X-L and that such expression may be a marker of chemoresistant disease.