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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Differential heat shock protein localization in chronic lymphocytic leukemia
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Differential heat shock protein localization in chronic lymphocytic leukemia

机译:慢性淋巴细胞白血病的差异热休克蛋白定位

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Mechanisms behind carcinogenesis and resistance of tumor cells to treatment regimes remain elusive. The major stress proteins Hsp72, Hsp90, and Hsp27 are credible candidates to provide this resistance, as their overexpression in many cancer types is well documented. In addition to being present inside tumor cells, where they confer resistance to apoptosis, Hsp72, in particular, is presented externally, embedded in the cell membrane of cancer cells. This study aimed to investigate the localization of Hsp72, Hsp90, and Hsp27 in leukocytes from patients with CLL and age-matched control subjects. CLL patients were found to express significantly higher levels of iHsp90 (CLL=2463 MFI; control=748 MFI) and iHsp27 (CLL=2190 MFI; control=1031 MFI) in lymphocytes than that expressed by lymphocytes from control subjects. Furthermore, expression of iHsp90 was shown to be related to stage of disease, and expression of iHsp27 correlated with levels of active caspase-3. Patients were found to express very high levels or very low levels of sHsp72 and iHsp72 in CD5+/CD19+ cells, although surface and intracellular datasets did not correlate. Levels of extracellular Hsp72 circulating in the serum were found to correlate with internal levels of Hsp72 and were also found to be significantly lower in patients receiving corticosteroid treatment than in patients not receiving corticosteroid treatment. Finally, analysis of the number of circulating Tregs revealed significantly elevated numbers in CLL patients compared with control subjects.
机译:致癌和肿瘤细胞对治疗方案的耐药性背后的机制仍然难以捉摸。主要应激蛋白Hsp72,Hsp90和Hsp27是提供这种抗药性的可靠候选者,因为它们在许多癌症类型中的过表达都有据可查。除了存在于肿瘤细胞内部,它们在其中赋予对细胞凋亡的抗性之外,尤其是Hsp72,是从外部存在的,嵌在癌细胞的细胞膜中。这项研究旨在调查Hsp72,Hsp90和Hsp27在CLL患者和年龄匹配的对照受试者的白细胞中的定位。发现CLL患者的淋巴细胞中iHsp90(CLL = 2463 MFI;对照= 748 MFI)和iHsp27(CLL = 2190 MFI;对照= 1031 MFI)的表达水平明显高于对照对象的淋巴细胞。此外,显示iHsp90的表达与疾病的发展阶段有关,而iHsp27的表达与活性caspase-3的水平有关。尽管表面和细胞内数据集没有相关性,但发现患者在CD5 + / CD19 +细胞中表达非常高水平或非常低水平的sHsp72和iHsp72。发现血清中循环的细胞外Hsp72水平与Hsp72的内部水平相关,并且发现接受皮质类固醇治疗的患者的Hsp72水平明显低于未接受皮质类固醇治疗的患者。最后,对循环中Tregs数量的分析显示,与对照对象相比,CLL患者的Treg数量显着增加。

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