title: Identification of cancer stem cells in a Tax-transgenic (Tax-Tg) mouse model of adult T-cell leukemia/lymphoma.
abstract: Adult T-cell leukemia/lymphoma (ATL) is a malignant lymphoproliferative disorder caused by HTLV-I infection. In ATL, chemotherapeutic responses are generally poor, which has suggested the existence of chemotherapy-resistant cancer stem cells (CSCs). To identify CSC candidates in ATL, we have focused on a Tax transgenic mouse (Tax-Tg) model, which reproduces ATL-like disease both in Tax-Tg animals and also after transfer of Tax-Tg splenic lymphomatous cells (SLCs) to nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Using a limiting dilution transplantation, it was estimated that one CSC existed per 10(4) SLCs (0.01%). In agreement with this, we have successfully identified candidate CSCs in a side population (0.06%), which overlapped with a minor population of CD38(-)/CD71(-)/CD117(+) cells (0.03%). Whereas lymphoma did not develop after transplantation of 10(2) SLCs, 10(2) CSCs could consistently regenerate the original lymphoma. In addition, lymphoma and CSCs could also be demonstrated in the bone marrow and CD117(+) CSCs were observed in both osteoblastic and vascular niches. In the CSCs, Tax, Notch1, and Bmi1 expression was down-regulated, suggesting that the CSCs were derived from Pro-T cells or early hematopoietic progenitor cells. Taken together, our data demonstrate that CSCs certainly exist and have the potential to regenerate lymphoma in our mouse model.
authors: Department of Safety Research on Blood and Biologics, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors: Jumpei
authors: J
authors: Yamazaki
authors: Takuo
authors: T
authors: Mizukami
authors: Kazuya
authors: K
authors: Takizawa
authors: Madoka
authors: M
authors: Kuramitsu
authors: Haruka
authors: H
authors: Momose
authors: Atsuko
authors: A
authors: Masumi
authors: Yasushi
authors: Y
authors: Ami
authors: Hideki
authors: H
authors: Hasegawa
authors: William W
authors: WW
authors: Hall
authors: Hajime
authors: H
authors: Tsujimoto
authors: Isao
authors: I
authors: Hamaguchi
authors: Kazunari
authors: K
authors: Yamaguchi
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D004195:Disease Models, Animal; D016355:Genes, pX / Q000502:physiology; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000473:pathology*; D008223:Lymphoma / Q000473:pathology; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000473:pathology*; D013160:Splenic Neoplasms / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins