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Molecular-pathological analysis of the transformation mechanism to overt leukemia of myelodysplastic syndromes

骨髓增生异常综合征显性白血病转化机制的分子病理学分析

基本信息

批准号：
08457059
负责人：
KAMIYAMA Ryuichi
金额：
$ 4.1万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457059/
关键词：
apoptosis cytokines myelodysplastic syndromes 白血病化機構分子病理学 tunor necrosis factor Pas抗原 Pas-ligand tumor necrosis factorα Epstein-Barr virus P^<53>遺伝子

项目摘要

1) Analysis of apoptosis in the bone marrow from patients with myelodysplastic syndromes (MDS)Hematopoietic cells of the bone marrow in MDS patients exhibited significantly-higher frequency of apoptosis compared with the cells in control individuals. In contrast, bone marrow of conventional de novo AML had only a few apoptotic cells.2) Character of bone marrow stromal cells in MDS patientsFresh frozen bone marrow samples of MDS cases were analyzed for the expression of various cytokines using RT-PCR method for mRNA and immunohistochemistry for protein production. The results indicated that MDS bone marrow macrophages over-expressed TNF-alpha and INF-gamma whereas expression of these cytokines was scarce in control bone marrow as well as in AML bone marrow.3) Fas/Fas-ligand system in the bone marrow of MDSTo clarify the contribution of Fas/Fas-ligand system in the induction of apoptosis in MDS bone marrow, RT-PCR analysis and immunohistochemical staining were performed. The expression of Fas was determined in the hematopoietic cells of MDS bone marrow while control and AML bone marrow exhibited negative signals. Further, Fas-ligand was expressed in hematopoietic cells as well as macrophages of the bone marrow of MDS.Thus, apoptotic signals by Fas/Fas-ligand system seemed to be transduced via hematopoietic-hematopoietic as well as hematopoietic-stromal cell interactions.

1)骨髓增生异常综合征(MDS)患者骨髓细胞凋亡率分析MDS患者骨髓造血细胞凋亡率明显高于正常对照组。2)MDS患者骨髓基质细胞的特征：采用RT-PCR方法检测MDS患者新鲜冰冻骨髓标本中各种细胞因子的表达，免疫组织化学方法检测MDS患者骨髓中各种细胞因子的表达。结果表明，MDS骨髓巨噬细胞高表达肿瘤坏死因子-α和干扰素-γ，而正常骨髓和AML骨髓中这两种细胞因子的表达较少。3)MDS骨髓Fas/Fas-Ligand系统在MDS骨髓细胞凋亡诱导中的作用。MDS骨髓造血细胞Fas表达阳性，而对照组和AML骨髓Fas表达阴性。此外，MDS的骨髓造血细胞和巨噬细胞均表达Fas-Ligand，因此，Fas/Fas-Ligand系统的凋亡信号可能通过造血细胞与造血细胞以及造血细胞与基质细胞的相互作用来传递。