2004 Fiscal Year Final Research Report Summary
Microarray Analyses of Molecular Pathways Associated with Pathogenesis
| Project/Area Number |
12204012
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | National Cancer Center Research Institute |
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Principal Investigator |
ICHIKAWA Hitoshi National Cancer Center Research Institute, Cancer Transcriptome Project, Project Leader, 腫瘍発現解析プロジェクト, プロジェクトリーダー (30201924)
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| Project Period (FY) |
2000 – 2004
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| Keywords | DNA microarray / gene expression profiling / transcription network / neutrophilic differentiation / molecular pathway / acute mveloid leukemia |
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| Research Abstract |
The main object of this work is to develop bases and tools to investigate molecular pathways associated with pathogenesis using gene expression profiles of clinical samples. To achieve this, we selected acute myeloid leukemia as a major target, and carried out following analyses.
1. Analysis of gene expression aberration induced by leukemic fusion transcription factors: We analyzed alterations in gene expression caused by ectopic expression of AML1-MTG8, and revealed that AML1-MTG8 induces partial differentiation into promyelocytes but inhibits terminal differentiation into mature granulocytes.
2. Analysis of gene expression alteration during neutrophilic differentiation: As a basis to investigate the mechanism to cause differentiation block in AML, we analyzed gene expression alteration during neutrophilic differentiation of a mouse myeloid cell line L-GM, which was induced by G-CSF stimulation or overexpression of a transcription factor C/EBPα, C/EBPε or PU.l. This analysis revealed th
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e existence of two distinguishable gene regulation pathways to proceed the differentiation.
3. Analysis of gene expression of AML clinical samples: We analyzed gene expression of 61 clinical samples obtained from pediatric AML patients. This analysis revealed that AML has gene expression patterns specific to the chromosomal translocations such as t(8;21) and inv(16), and identified a gene expression signature that are associated with prognosis of pediatric AML.
4. Development of a pathway analysis tool: We developed a tool to estimate the activation status of the molecular pathways by comparing the expression of the pathway-specific genes that were identified in "Analysis 2". This enabled us to predict genetic aberrations to cause differentiation block in AML.
5. Analysis of genes associated with oncogenic transformation: As a basis to investigate malignant tumors other than leukemia, we analyzed gene expression alteration induced by Src transformation, and identified genes involved in anchorage-independent growth and cell motility. Less
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