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

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461415
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto 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