2015 Fiscal Year Final Research Report
Identification of the novel therapeutic target molecules for leukemia stem cells based on TIM-3/galectin-9 interaction
| Project/Area Number |
26713034
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Partial Multi-year Fund |
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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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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Keywords | 白血病幹細胞 / 急性骨髄性白血病 / がん幹細胞 / TIM-3 |
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| Outline of Final Research Achievements |
T-cell immunoglobulin mucin-3 (TIM-3) is expressed on surface of self-renewing leukemic stem cells (LSCs) in acute myeloid leukemia (AML). Here we show that TIM-3 and its ligand, galectin-9 (Gal-9), constitute an autocrine loop critical for human AML LSC development. Serum Gal-9 was significantly elevated in primary AML patients and in mice xenografted with human AML. Neutralization of Gal-9 inhibited xenogeneic reconstitution of human AML, and Gal-9 ligation of TIM-3 co-activated NF-κB and β-catenin signaling, suggesting that TIM-3 signaling is necessary for LSC self-renewal. Interestingly, identical changes were progressively involved in transformation into myeloid leukemia from a variety of pre-leukemic disorders. Thus, molecules constituting the TIM-3/Gal-9 autocrine loop could be therapeutic targets applicable to most types of myeloid leukemia.
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| Free Research Field |
造血器腫瘍
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