Analyzing the mechanisms underlying ATL leukemogenesis and identifying new markers of ATL stem cell using ATL humanized mice

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591383
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: The University of Tokyo
• Principal Investigator: YAMOCHI Tadanori 東京大学, 新領域創成科学研究科, 特任研究員 (80306844)
• Co-Investigator(Kenkyū-buntansha): WATANABE Nobukazu 九州がんセンター, 細胞治療科, 医長 (10334278)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: Adult T cell leukemia / Cancer stem cells / Tumor initiating cells

Outline of Final Research Achievements

We have been searching for cancer stem cells (CSCs) of adult T cell leukemia (ATL). We have defined CSCs in the tumor as tumorigenic cells capable of dividing into tumorigenic cells and non-tumorigenic cells, which can be distinguished based on their cell surface markers and serial transplantablity in immunodeficient mice. We successfully established a number of serially transplanted cell lines by intra-liver transplantation of PBMC from ATL patients into NOJ mice. One of the cell lines, derived from CD4+ CCR4+ sorted cells showed ATL-like phenotypes such as the infiltration into spleen, liver, lung and born marrow, and the surface markers of CD4+, CCR4+, CD5+, cytoplasmic CD3+ and surface CD3-. This cell line harbored complicated chromosomal abnormalities including t (11, 14) translocation and a partial trisomy of chromosome 14. We have identified candidate markers that can discriminate the tumorigenic cells from non-tumorigenic cells in the CD4+ CCR4+ transplanted cell line.

Free Research Field

腫瘍学