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2014 Fiscal Year Final Research Report

Novel therapeutics targeting the specified metabolic pathway and transcription factor related to stem cells of chronic myelogenous leukemia

Research Project

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Project/Area Number 24390244
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Hematology
Research InstitutionKyoto University

Principal Investigator

MAEKAWA TAIRA  京都大学, 医学(系)研究科(研究院), 教授 (80229286)

Co-Investigator(Kenkyū-buntansha) MIURA Yasuo  京都大学, 医学研究科, 助教 (70605146)
Co-Investigator(Renkei-kenkyūsha) HIRAI Hideyo  京都大学, 医学研究科, 助教 (50315933)
Project Period (FY) 2012-04-01 – 2015-03-31
Keywords白血病幹細胞 / 慢性骨髄性白血病 / 低酸素 / C/EBPβ
Outline of Final Research Achievements

Leukemic stem cell hide in hypoxic bone marrow microenvironment and causes therapy resistance and the recurrence. Chronic myelogenous leukemia (CML) stem cells stay in G0 cell-cycle state. CML stem cells alive in such circumstances independent from BCR-ABL expression, so that they are hard to become the target of tyrosine kinase inhibitors (TKI). We found that transcription factor C/EBPβ acted toward differentiation of CML stem cells, and its expression was low in hypoxia. We hypothesized when the expression of C/EBPβ were low, CML stem cells would remain in the G0 state in hypoxia. We found that interferon α (IFN α), independently from BCR-ABL expression, enhanced the expression of C/EBPβ of CML stem cells through STAT5 pathway. In conclusion, IFN α could drive CML stem cells into cell-cycle state by enhancing their expression of C/EBPβ and differentiate them. These differentiated from CML stem cells proliferate in BCR-ABL dependent fashion, and could become the target of TKI.

Free Research Field

血液内科学

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Published: 2016-06-03  

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