The Role Of Osteoclasts In the developing Leukemic Stem Cell Niche in a Mouse Model of Adult T-Cell Leukemia

2016 Fiscal Year Final Research Report

• Project/Area Number: 25461440
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Mizukami Takuo 国立感染症研究所, 血液・安全性研究部, 室長 (60415487)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 癌幹細胞 / ニッチ / 微小環境 / 破骨細胞 / 骨浸潤抑制 / Zoledronic acid

Outline of Final Research Achievements

Adult T cell leukemia (ATL) is a lymphoproliferative disorder caused by infection with HTLV-I. Although various chemotherapies have shown significant complete remission rates, most of the treated patients relapse. These data indicate the existence of leukemic stem cells (LSCs) and a specific niche that protects from chemotherapies. We identified that ATL-LSCs have reproduced the original tumor. Using homing assay, we found that more than 60% of first colonized cells in the spleen and BM were AT-LSCs and ATL-LSCs were also attached to the reticular cells in the trabecular bone. We also found the number of osteoclast was significantly increased at the trabecular region. To clarify the role of osteoclast, we treated osteoclast inhibitor Zoledronic acid. As a result, ATL cells were dramatically reduced in the BM and extend the mouse survival rate significantly in this treatment. These data suggest osteoclast have a potential therapeutic target in the mouse model of ATL.

Free Research Field

血液内科学