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FK506结合蛋白51(FKBP51)在特发性骨髓纤维化和非肿瘤性造血来源的骨髓细胞及巨核细胞中的组成性表达。

Constitutive expression of the FK506 binding protein 51 (FKBP51) in bone marrow cells and megakaryocytes derived from idiopathic myelofibrosis and non-neoplastic haematopoiesis.

作者信息

Bock Oliver, Neusch Michael, Büsche Guntram, Mengel Michael, Kreipe Hans

机构信息

Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany.

出版信息

Eur J Haematol. 2004 Apr;72(4):239-44. doi: 10.1046/j.0902-4441.2003.00204.x.

Abstract

OBJECTIVES

Overexpression of FK506 binding protein 51 (FKBP51) in megakaryocytic progenitor cells generated from purified CD34+ cells in patients with idiopathic myelofibrosis (IMF) has been demonstrated. It has been suggested that FKBP51 is involved in the dysregulation of the apoptotic programme with consecutive prolongation of cell survival. The knowledge of FKBP51 and its expression in bone marrow cells and mature megakaryocytes in non-neoplastic haematopoiesis and IMF is sparse.

METHODS

To evaluate a potential overexpression of FKBP51 in patients with IMF (n = 37) compared with non-neoplastic haematopoiesis (n = 31), total bone marrow cells as well as single megakaryocytes, isolated by laser microdissection, were quantitatively analysed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). By applying immunohistochemistry, FKBP51 gene expression was correlated with staining pattern and cellular localisation of the corresponding FKBP51 protein.

RESULTS

We demonstrated that FKBP51 is constitutively expressed in non-neoplastic haematopoiesis. FKBP51 gene expression by total bone marrow cells as well as megakaryocytes was not significantly different in IMF. FKBP51 protein expression could be localised to myeloid progenitor cells as well as megakaryocytes. In particular, megakaryocytes were stained almost exclusively nuclear for FKBP51. No differences in expression patterns between both IMF and control cases could be demonstrated.

CONCLUSIONS

For the first time, FKBP51 expression, in particular gene expression and subcellular localization was described in bone marrow cells of non-neoplastic and neoplastic haematopoiesis grown in vivo. We conclude that FKBP51 could be temporarily overexpressed in megakaryocytic progenitors rather than contribute to the accumulation of mature megakaryocytes in IMF.

摘要

目的

已证实在特发性骨髓纤维化(IMF)患者中,由纯化的CD34+细胞生成的巨核细胞祖细胞中FK506结合蛋白51(FKBP51)过表达。有人提出FKBP51参与凋亡程序失调,导致细胞存活时间持续延长。关于FKBP51及其在非肿瘤性造血和IMF的骨髓细胞及成熟巨核细胞中的表达情况,目前了解较少。

方法

为评估与非肿瘤性造血(n = 31)相比,IMF患者(n = 37)中FKBP51是否存在潜在过表达,通过实时逆转录聚合酶链反应(RT-PCR)对经激光显微切割分离的全骨髓细胞以及单个巨核细胞进行定量分析。应用免疫组织化学方法,将FKBP51基因表达与相应FKBP51蛋白的染色模式和细胞定位相关联。

结果

我们证明FKBP51在非肿瘤性造血中组成性表达。在IMF中,全骨髓细胞以及巨核细胞的FKBP51基因表达无显著差异。FKBP51蛋白表达可定位于髓系祖细胞以及巨核细胞。特别是,巨核细胞中FKBP51几乎仅在细胞核中染色。未发现IMF与对照病例之间在表达模式上存在差异。

结论

首次描述了在体内生长的非肿瘤性和肿瘤性造血的骨髓细胞中FKBP51的表达情况,特别是基因表达和亚细胞定位。我们得出结论,FKBP5可能在巨核细胞祖细胞中暂时过表达,而不是导致IMF中成熟巨核细胞的积累。

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