Characiterization of ATL stem cell candidates in HBZ transgenic mouse model

KAKEN

About This Project

Japan Grant Number
JP16K09833 (JGN)
Funding Program
Grants-in-Aid for Scientific Research
Funding Organization
Japan Society for the Promotion of Science

Kakenhi Information

Project/Area Number
16K09833
Research Category
Grant-in-Aid for Scientific Research (C)
Allocation Type
  • Multi-year Fund
Review Section / Research Field
  • Biological Sciences > Medicine, Dentistry, and Pharmacy > Clinical internal medicine > Hematology
Research Institution
  • National Institute of Infectious Diseases
Project Period (FY)
2016-04-01 〜 2020-03-31
Project Status
Completed
Budget Amount*help
4,680,000 Yen (Direct Cost: 3,600,000 Yen Indirect Cost: 1,080,000 Yen)

Research Abstract

Human T cell leukemia virus-1 (HTLV-1) is a T cell tropic retrovirus that causes Adult T cell leukemia (ATL). ATL has worse prognosis than other T cell malignancies. We hypothesized the existence of chemotherapy resistant cancer stem cell in ATL. In previous studies, we have newly identified ATL stem cells (ATLSCs) candidate in the Tax transgenic (Tg) mouse model (Blood, 2009). In this study, we also found HBZ-Tg derived ATLSCs could not colonize and proliferate in the c-kit ligand, membrane bound SCF mutant mouse (Sl/Sld) and in the presence of SCF neutralizing antibody ACK2. These data clearly suggested that SCF-c-kit signaling is essential to colonize and initiating ATL in the mouse model. We also found CCL3, CCL4, IL-4, IL-9, and IL-10 are highly produced in the ATLSCs microenvironment. These data suggested that these cytokines environment synergistically regulate ATLSC function and leukemic niche.

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