| Project/Area Number |
22890043
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAKAHARA Fumio The University of Tokyo, 医科学研究所, 助教 (80581181)
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| Project Period (FY) |
2010
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| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥1,599,000 (Direct Cost: ¥1,230,000、Indirect Cost: ¥369,000)
Fiscal Year 2010: ¥1,599,000 (Direct Cost: ¥1,230,000、Indirect Cost: ¥369,000)
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| Keywords | 白血病 / 白血病幹細胞 / 慢性骨髄性白血病 / 急性転化 |
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| Research Abstract |
We show here that Hairy enhancer of split 1 (Hes1) has a role in blast crisis transition of CML. Hes1 is a basic helix-loop-helix transcriptional repressor that affects differentiation and often helps maintain cells in an immature state in various tissues. Also we show that expression of Hes1 immortalizes common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs). Whereas these cells did not develop myeloproliferative neoplasms when intravenously administered into irradiated mice, combination of Hes1 and BCR-ABL in both CMPs and GMPs caused a blast crisis of human CML-like disease, resulting in the rapid death of all the recipient mice. Intriguingly, Hes1 was highly expressed in 8 of 20 patients with CML in blast crisis, but not in the chronic phase, and dominant negative Hes1 retarded the growth of some CML cell lines expressing Hes1. These results taken together suggest that our model provides a good model to study mechanisms of the blast crisis transition in CML.
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