2021 Fiscal Year Final Research Report
Serine protease expression and its biological significance in AML
Project/Area Number |
19K08810
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | Nagoya University |
Principal Investigator |
Ishikawa Yuichi 名古屋大学, 医学部附属病院, 病院講師 (80721092)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 造血器腫瘍 / 急性骨髄性白血病 / セリンプロテアーぜ / 好中球エステラーゼ / 細胞内シグナル伝達 |
Outline of Final Research Achievements |
Acute myeloid leukemia (AML) is still one of the refractory malignant diseases and relapsed in more than half of patients. We identified high expression of neutrophil elastase gene which encoded serine protease and its abnormal transcripts in recurrent AML specimens by RNA sequence analysis. The purpose of this study was to elucidate the clinical and biological significance of the expression of serine protease genes in AML. In patient samples, leukemic cell differentiation and cell lineage and PRTN3 gene expression was closely associated. In addition, the deletion of the PRTN3 gene in cell lines and mouse leukemia model affected the onset of AML and leukemia cell proliferation through the downregulation of signal transduction pathways and suggested the potency of PRTN3 gene as a therapeutic target for AML treatment.
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Free Research Field |
造血器腫瘍
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Academic Significance and Societal Importance of the Research Achievements |
本研究は、難治性AML試料から同定した好中球エラスターゼ発現の臨床的、生物学的意義について解析を行い、AML発症に関連する分化、融合遺伝子や遺伝子変異と好中球エラスターゼ高発現との関わりについて明らかにした。また、本研究では、同分子が細胞内シグナル伝達経路と関連してAMLの発症進展に重要である事も示し、AMLの発症基盤および治療抵抗因子の解明、新規疾患層別化とその克服につながる成果が得られた。さらに、好中球エラスターゼは、造血器腫瘍以外の悪性腫瘍では殺細胞効果を示すとされ、同分子とその周辺シグナル経路との関わりの解明は、造血器腫瘍のみならず固形腫瘍における新規治療法への発展も考えられる。
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