| Project/Area Number |
15591012
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Nagasaki University |
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Principal Investigator |
TSUKASAKI Kunihiro Nagasaki Univ., Graduate School of Med., Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (40274659)
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| Co-Investigator(Kenkyū-buntansha) |
TOMONAGA Masao Nagasaki Univ., Graduate School of Med., Professor, 大学院・医歯薬学総合研究科, 教授 (40100854)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | adult T-cell leukemia / lymphoma / human T-lymphotropic virus type-1 / multi-step carcinogenesis / chromosomal instability / expression profile / comprehensive analysis |
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| Research Abstract |
Adult T-cell leukemia/lymphoma(ATL) is associated with human T-lymphotropic virus type-1(HTLV-1). To understand the changes in expression that occur in the progression of chronic phase of ATL to acute crisis, the gene expression profiles of fresh ATL cells were compared in 4 pairs of samples (progression of chronic to acute phase in 3 patients, as well as one typical chronic phase sample versus one typical acute phase sample) using high density oligonucleotide DNA arrays. We identified 203 genes that were commonly up-regulated in acute versus chronic phase samples including ribosomal proteins, proteosome subunits, eukaryotic translation factors, immunophilins, heat shock proteins and genes important for DNA replication. Additionally, we identified 91 commonly down-regulated genes including immune molecules related to MHC and a phosphatase. Several of the genes were previously identified to be associated with the Tax protein of HTLV-1. Some of the up-regulated genes were located in amplified regions identified by comparative genomic hybridization in the corresponding chronic/acute ATL sample. Using real-time quantitative PCR, we confirmed the array-results in those specimens analyzed by microarray. These results demonstrated that distinct sets of genes that are known to be critical in cellular transformation and/or activation as well as chromosomal instability are up- or down-regulated during the transition to the acute phase of ATL.
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