| Project/Area Number |
12470202
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Nagoya City University |
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Principal Investigator |
UEDA Ryuzo Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (20142169)
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| Co-Investigator(Kenkyū-buntansha) |
IIDA Shinsuke Nagoya City University, Graduate School of Medical Sciences, Assistant professor, 大学院・医学研究科, 講師 (50295614)
WAKITA Atsushi Nagoya City University, Graduate School of Medical Sciences, Associate Professor, 大学院・医学研究科, 助教授 (20264715)
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| Project Period (FY) |
2000 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | multiple myeloma / chromosomal translocation / t(14;20)(q32;q11) / MAFB / t(1;14)(q34;q32) / E3 / LAPTm5 / MGUS / developmental pathway / 定量PCR / 病型 / 進展 / Multiple Myeloma / Chromosomal Translocation / FISH / Real time PCR / MUM1 / IRF4 / LAPTM5 / Cyclin D1 / 二重色FISH法 / t(1;14)(p36;q32) / Ku80 |
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| Research Abstract |
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.
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