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2015 Fiscal Year Final Research Report

Maintenance of CML stem cells through regulation of C/EBPbeta transcription factor

Research Project

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Project/Area Number 25461415
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionKyoto University

Principal Investigator

Hirai Hideyo  京都大学, 医学(系)研究科(研究院), 助教 (50315933)

Co-Investigator(Renkei-kenkyūsha) MINAMISHIMA Yoji  慶應義塾大学, 医学部, 講師 (20593966)
MAEKAWA Taira  京都大学, 医学研究科, 教授 (80229286)
YOKOTA Asumi  京都大学, 医学研究科, 研究員 (00571556)
Project Period (FY) 2013-04-01 – 2016-03-31
Keywords白血病幹細胞 / 低酸素 / 転写因子 / 慢性骨髄性白血病 / C/EBPbeta
Outline of Final Research Achievements

In order to achieve complete cure of chronic myeloid leukemia (CML), eradication of CML stem cells (CML-SCs) is cruicial.
In this study, we focused on hypoxic microenvironment and regulation of the transcription factor C/EBPbeta, which is activated by BCR-ABL and promotes differentiation and exhaustion of CML-SCs. Hypoxic condition in vitro reduced the expression of C/EBPbeta in CML cell lines, and cytokine treatment could not reverse this effect. In contrast, when the mice, which had been transplanted with BCA-ABL expressing bone marrow cells, were treated with cytokines, exhaustion of CML-SCs were promoted via upregulation of C/EBPbeta. These results suggest that cytokine treatment may eradicate CML-SCs by remodeling bone marrow microenvironment including hypoxia in addition to direct action on CML-SCs.

Free Research Field

血液学

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Published: 2017-05-10   Modified: 2018-02-02  

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