Role of metabolic regulation in leukemia stem cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19548
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Kanazawa University
• Principal Investigator: Ohta Kumiko 金沢大学, がん進展制御研究所, 博士研究員 (30416177)
• Research Collaborator: HIRAO ATSUSHI 金沢大学, がん進展制御研究所, 教授 (90343350)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 白血病 / FOXO / 細胞分化 / 解糖系

Outline of Final Research Achievements

Myeloid leukemias are essentially hematopoiesis gone awry at hematopoietic stem cells(HSCs)/progenitor cells. Forkhead members of the class O transcription factor (FOXO), plays a critical role of maintenance of HSCs, leukemia initiating cells. In this study, we attempted to establish a system for identification of molecules regulating differentiation blockade of leukemia stem cells by monitoring FOXO activity. Analysis of effects of the pharmaceutical inactivation of FOXO on leukemia differentiation revealed unique FOXO function in maintaining LSCs and coupling it with cellular metabolism. FOXO inhibition induced glycolysis and consequently increased apoptosis and cell differentiation, thereby suppressing tumor formation in vivo. These results indicate that FOXO is involved in metabolic reprograming and differentiation in LSCs, and thus is a promising target for leukemia.

Free Research Field

細胞生物学