权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Analysis of Molecular Mechanism of Blastic Crisis in Chronic Myelocytic Leukemia

慢性粒细胞白血病原始细胞危象的分子机制分析

基本信息

批准号：
07042002
负责人：
HIRAI Hisamaru
金额：
$ 3.65万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1995
资助国家：
日本
起止时间：
1995 至无数据
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07042002/
关键词：
Chronic Myelocytic Leukemia Blastic Crisis Evi-1 Gene Cell Cycle p16INK4A Gene p53 Gene RB Protein Tumor Suppressor Gene

项目摘要

Evi-1 is a transforming gene originally identified in a common integration site of murine leukemia retrovirus and mapped in human chromosome 3q26. It is overexpressed in retrovirus induced murine myeloid leukemias as well as human myeloid leukemias with 3q26 abnormalities, and thus thought to be responsible for both human and murine leukemogenesis. In this study, a possible involvement of the Evi-1 gene in blastic transformation of chronic myelocytic leukemia (CML) was examined by northern blot analysis, and the frequencies of its expression were compared between Japanese patients and American ones. Expression of the Evi-1 gene was detected in 48% of Japanese patients and 40% of American ones. Our results suggest that increased expression of the Evi-1 gene may play an important role in development of human leukemias, especially in progression from chronic phase to blastic crisis of CML even without 3q26 abnormalities.It is now evident that the cell cycle machinery has a variety of elem … More ents negatively regulating cell cycle progression. Among these negative regulators in cell cycle control, however, only 4 have been shown to be consistently involved in development of human cancers as tumor suppressors : Rb (Retinoblastoma susceptibility protein), p53, and recently identified two cyclin-dependent kinase inhibitors, p16INK4A/MTS1 and p15INK4B/MTS2. Because there are functional interrelations among these negative regulators in the cell cycle machinery, it is particularly interesting to investigate the multiplicity of inactivations of these tumor suppressors in blastic transformation of CML.In order to address this point, we examined inactivations of these four genes in patients with blastic crisis of CML by Southern blot and PCR-SSCP analyzes. We also analyzed Rb protein expression by western blot analysis. The p16INK4A was homozygously deleted in 9% and 15% in Japanese patients and American ones. The p53 gene was mutated in 27% and 20%, and the RB protein was inactivated in 18% and 14% in Japanese patients and American ones, respectively. These results suggest that there are no significant differences in inactivation frequences of these tumor suppressors in blastic transformation of CML. Less

Evi-1是一个转化基因，最初在鼠白血病逆转录病毒的一个共同整合位点被鉴定，并定位在人染色体3q 26。它在逆转录病毒诱导的鼠髓性白血病以及具有3q 26异常的人髓性白血病中过表达，因此被认为是人和鼠白血病发生的原因。本研究通过北方印迹分析检测了Evi-1基因可能参与慢性粒细胞白血病（CML）的母细胞转化，并比较了日本患者和美国患者之间Evi-1基因的表达频率。在48%的日本患者和40%的美国患者中检测到Evi-1基因的表达。我们的研究结果表明Evi-1基因表达的增加在人类白血病的发展中起重要作用，特别是在慢性期向急变期的进展中，即使没有3q 26异常。 ...更多信息负调节细胞周期进程。然而，在这些细胞周期控制中的负调节因子中，只有4种被证明作为肿瘤抑制因子始终参与人类癌症的发展：Rb（视网膜母细胞瘤易感蛋白），p53，以及最近鉴定的两种细胞周期蛋白依赖性激酶抑制剂，p16 INK 4A/MTS 1和p15 INK 4 B/MTS 2。由于这些负调控因子在细胞周期机制中存在功能上的相互关系，因此研究这些肿瘤抑制因子在CML急变中的多重失活是特别有趣的，为了解决这一点，我们通过Southern印迹和PCR-SSCP分析检测了CML急变患者中这四个基因的失活。我们还分析了Rb蛋白表达的Western印迹分析。日本和美国患者p16 INK 4A基因的同源性缺失率分别为9%和15%。日本和美国患者中p53基因突变率分别为27%和20%，RB蛋白失活率分别为18%和14%。这些结果表明，在CML急变过程中，这些抑癌基因的失活频率无显著差异。少