2009 Fiscal Year Final Research Report
Cancer stem cells and genes responsible for their development in hematopoietic system
| Project/Area Number |
17109010
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Kyushu University |
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Principal Investigator |
AKASHI Koichi Kyushu University, 大学院・医学研究院・病態修復内科学, 教授 (80380385)
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| Co-Investigator(Kenkyū-buntansha) |
TESHIMA Takanori 九州大学, 大学病院, 准教授 (40284096)
MIYAMOTO Toshihiro 九州大学, 大学病院, 講師 (70343324)
TANAKA Shinji 東京医科歯科大学, 大学病院, 特任准教授 (30253420)
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| Project Period (FY) |
2005 – 2009
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| Keywords | 造血器腫瘍 / 腫瘍性幹細胞 / 急性骨髄性白血病 / 慢性リンパ性白血病 |
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| Research Abstract |
We identified leukemia stem cells (LSC) of acute myelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL) using multi-colored FACS and xenotransplant system with severe immune-deficient mice. We identified high expression of TIM-3 in LSC population, but not hematopoietic stem cells (HSC). Treatment with anti-TIM-3 antibody markedly reduced leukemic repopulation, but did not affect reconstitution of normal HSCs. We also found that MCL-1 play a critical role in maintenance of LSC via FLT3 signaling and acquisition of FLT3 abnormality ensures LSC survival by upregulating MCL-1 via constitutive STAT5 activation. We also have shown that primary oncogenic event in CLL involves hematopoietic stem cells, and development of CLL might depend on clonal selection by abnormal BCR signaling mutations follow to become overt CLL.
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Research Products
(63 results)
