2014 Fiscal Year Final Research Report
Target TIM-3 to eradicate AML stem cells
| Project/Area Number |
23390254
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
AKASHI Koichi 九州大学, 大学院医学研究院, 教授 (80380385)
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| Project Period (FY) |
2011-04-01 – 2015-03-31
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| Keywords | 白血病 / 幹細胞 / TIM-3 / 標的治療 |
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| Outline of Final Research Achievements |
We have previously reported that T-cell immunoglobulin mucin-3 (TIM-3) is expressed on surface of self-renewing leukemic stem cells (LSCs) in acute myeloid leukemia (AML). In this study, we focused on TIM-3 ligands including galectin-9 and HMGB-1 to clarify the function of TIM-3 in human AML. Here, we show that TIM-3 and its ligand, galectin-9, constitutes an autocrine loop critical for human AML LSC development; galectin-9 is highly expressed in primary AML/LSCs, and these AML/LSCs secrete galectin-9 in an autocrine manner. Furthermore, we found that TIM-3/galectin-9 interaction induced the activation of NF-kB pathway in primary TIM-3+ AML cells. These results collectively suggest that TIM-3 and galectin-9 constitutes very unique autocrine stimulatory signaling machinery, which should contribute to the cell autonomous activation of NF-kB pathway in primary AML/LSCs.
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| Free Research Field |
血液内科学
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