Budget Amount *help |
¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2013: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2011: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
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Outline of Final Research Achievements |
(1) We performed metabolomic analysis in hematopoietic stem cells (HSCs) and found that HSCs generate adenosine-5'-triphosphate by anaerobic glycolysis through a pyruvate dehydrogenase kinase (Pdk)-dependent mechanism. Loss of both Pdk isozymes attenuated HSC phenotypes including cell cycle. Thus, glycolytic metabolic status governed by Pdk acts as a cell cycle checkpoint that modulates HSCs. (2) Using a CML-like mouse model of myeloproliferative disease, we demonstrate that CML LICs can be divided into CD25(+)FcεRIα(-) Lineage marker (Lin)(-) Sca-1(+)c-Kit(+) (F(-)LSK) cells and CD25(-)F(-)LSK cells. The CD25(+)F(-)LSK cells had multilineage differentiation capacity, with a preference toward cytokine-producing mast cell commitment. The CD25(+)F(-)LSK cells exhibited higher LIC capacity. Our findings suggest that interleukin-2 derived from the microenvironment and CD25 expressed on CML LICs constitute a novel signaling axis that could be preferentially targeted in therapy for CML.
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