2015 Fiscal Year Final Research Report
Targeting malignant stem cells in BCR-ABL positive leukemia
Project/Area Number |
25461424
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Kyushu University |
Principal Investigator |
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Keywords | 慢性骨髄性白血病 |
Outline of Final Research Achievements |
In the present study, we got several important findings about the property of CML stem/progenitor cells. First, the frequencies of BCR-ABL positive clone in CD34+CD38- stem cell fraction varied from only 1% to 100% at diagnosis, suggesting that CML stem cells do not necessarily outgrow normal stem cells. On the other hand, the common myeloid progenitor (CMP) fraction markedly expanded in all cases, and the majority of these cells were positive for BCR-ABL FISH, indicating that the growth advantage of CML clone is obtained at the CMP stage. Importantly, leukemic CMPs suppressed the expression of IRF8, a transcription factor in the granulocyte lineage, which might play some role in the cell proliferation. The frequencies of BCR-ABL positive clone in the stem cell fraction strongly correlated with Sokal scores and, more interestingly, with the numbers of megakaryocyte progenitors, suggesting that “megakaryocyte niche” play some role in the survival and self-renewal of CML stem cells.
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Free Research Field |
造血幹細胞
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