2017 Fiscal Year Final Research Report
Identification of molecular mechanisms activating hematopoietic stem cells by monitoring expression levels of a new stem-cell marker ESAM
| Project/Area Number |
15K09475
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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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| Research Field |
Hematology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
金倉 譲 大阪大学, 医学系研究科, 教授 (20177489)
織谷 健司 国際医療福祉大学, 医学部, 教授 (70324762)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 造血幹細胞 / 白血病幹細胞 |
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| Outline of Final Research Achievements |
We previously demonstrated that the endothelial-cell selective adhesion molecule (ESAM) is an important marker of HSCs in humans. In the present study, we have exploited ESAM expression levels as an index to analyze the molecular mechanisms regulating the status of hematopoietic stem cells, and have applied findings to develop new strategies for diagnosis and treatment of human acute leukemia. Our study has revealed that many of human acute myeloid leukemia cases highly expressed ESAM on their tumor cells. We also found that leukemia stem cells (LSCs) represent ESAM expression, of which levels are heterogeneous and are fluctuating at single cell levels according to the proliferating status of LSCs. The TGFβ signaling pathway is autonomously involved in inducing heterogeneity in ESAM expression in the LSC population. The fluctuation is thought to confer certain benefits to LSCs, such as drug resistance and promoting invasiveness.
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| Free Research Field |
血液内科学
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