Development of the optimal therapies based on molecular genetics of multiple myeloma

基于多发性骨髓瘤分子遗传学的最佳疗法的开发

基本信息

批准号：
12470202
负责人：
UEDA Ryuzo
金额：
$ 7.74万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2003
项目状态：
已结题

项目摘要

1.Identification of novel chromosomal translocations found in multiple myeloma :1)t(1;14)(p34;q32) : 1p34 breakpoint of ODA cells was isolated by genomic cloning and found to have disrupted E3/LAPTm5 gene in terms of its expression. This phenomenon was caused by hypermethylation of the regulatory sequences of the gene.2)t(1;14)(p34;q32) : 1p34 breakpoint of ODA cells was isolated by genomic cloning and found to have disrupted E3/LAPTm5 gene in the first intron. Interestingly, this gene was shut off in 60% of the myeloma cell lines in terms of its expression. This phenomenon was caused by hypermethylation of the regulatory sequences of the gene.2.14q32 translocations in MGUS/smoldering multiple myeloma(SMM)Purified plasma cells derived from 16 MGUS/SMM patients were examined concerning 14q32 chromosomal trans locations by means of double color-FISH analysis. 56% of the cases carried 14q32 translocations, in which two thirds were between 14q32(IgH) and 11q13(CCND1) loci with concomitant nuclear expression of CyclinD1.3.Identification of the distinct developmental pathways of multiple myeloma :Quantitative RT-PCR assay was established for CCND1, FGFR3, MUM1, c-MAF, MAFB and c-MYC genes, and applied for the study of 19 cell lines and 30 myeloma samples. It led to the identification of at least three distinct developmental pathways of multiple myeloma, which originated from altered expression of CCND1, FGFR3 and c-MAF/MAFB genes.

1.多发性骨髓瘤中发现的新型染色体易位的鉴定：1)t(1;14)(p34;q32)：通过基因组克隆分离ODA细胞的1p34断点，发现其表达破坏了E3/LAPTm5基因。这种现象是由基因调控序列的高甲基化引起的。2)t(1;14)(p34;q32)：通过基因组克隆分离出ODA细胞的1p34断点，发现在第一个过程中破坏了E3/LAPTm5基因内含子。有趣的是，该基因在 60% 的骨髓瘤细胞系中表达被关闭。这种现象是由该基因调控序列的高甲基化引起的。2.MGUS/冒烟型多发性骨髓瘤(SMM)中的14q32易位通过双色FISH检查了16名MGUS/SMM患者的纯化浆细胞的14q32染色体易位。分析。 56% 的病例携带 14q32 易位，其中三分之二位于 14q32(IgH) 和 11q13(CCND1) 位点之间，同时核表达 CyclinD1.3。多发性骨髓瘤不同发育途径的鉴定：定量 RT-PCR 检测为 CCND1、FGFR3、MUM1、c-MAF、MAFB 和c-MYC基因，并应用于19个细胞系和30个骨髓瘤样本的研究。它导致了多发性骨髓瘤至少三种不同发育途径的鉴定，这些途径源于 CCND1、FGFR3 和 c-MAF/MAFB 基因表达的改变。