| Project/Area Number |
19K08874
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Arner Erik 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (20571839)
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| Co-Investigator(Kenkyū-buntansha) |
萩原 將太郎 東京女子医科大学, 医学部, 非常勤講師 (50306635)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | multiple myeloma / CAGE profiling / differential expression / Transcriptome analysis / Cell purification / Cell sample collection / Multiple Myeloma / NK cells / sSLAMF7 / CAGE |
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| Outline of Research at the Start |
Multiple myeloma is an intractable disease. Evasion of the immune system may be a reason of treatment resistance. The sSLAMF7 protein has been found in the serum of myeloma patients. We will study the effect of sSLAMF7 on natural killer (NK) cells in multiple myeloma patients.
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| Outline of Final Research Achievements |
Human primary natural killer cells (NK cells) were prepared from peripheral blood of Multiple Myeloma patients and healthy volunteers. The cohort consisted of 20 Multiple Myeloma patients and 10 healthy donors. The Multiple Myeloma patients were divided into two groups: 10 with high sSLAMF7 serum levels (fresh/relapsed cases) and 10 with low levels (remission or stable cases). RNA was extracted and gene expression was compared between the three groups using Cap Analysis of Gene Expression (CAGE) technology, which allows for base pair resolution detection and expression quantification of promoter regions. Differentially expressed genes were identified and subjected to Motif Activity Response Analysis (MARA) to identify putative regulators of observed changes in the transcriptional program of NK cells of Multiple Myeloma patients.
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| Academic Significance and Societal Importance of the Research Achievements |
Poor outcome in Multiple Myeloma (MM) patients with high sSLAMF7 serum levels may be linked to changes in NK cell gene expression programs. We aimed to reconstruct the NK cell transcriptional regulatory network that governs MM and is modulated by sSLAMF7, paving the way for novel therapeutic targets
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