@article{oai:repo.qst.go.jp:00047860,
 author = {Kuribayashi, Wakako and Takizawa, Kazuya and Sugata, Kenji and Kuramitsu, Madoka and Momose, Haruka and Sasaki, Eita and Hiradate, Yuki and Furuhata, Keiko and Asada, Yoshihisa and Iwama, Atsushi and Matsuoka, Masao and Mizukami, Takuo and Hamaguchi, Isao and 滝澤 和也},
 issue = {32},
 journal = {Oncotarget},
 month = {Jun},
 note = {Adult T-cell leukemia (ATL) is a malignant disease caused by human T-lymphotropic virus type 1. In aggressive ATL, the response to chemotherapy is extremely poor. We hypothesized that this poor response is due to the existence of chemotherapy-resistant cells, such as leukemic stem cells. Previously, we successfully identified an ATL stem cell (ATLSC) candidate as the c-kit+/CD38−/CD71− cells in an ATL mouse model using Tax transgenic mice. Here, with a new ATL mouse model using
HBZ-transgenic mice, we further discovered that the functional ATLSC candidate,
which commonly expresses c-kit, is drug-resistant and has the ability to initiate tumors and reconstitute lymphomatous cells. We characterized the ATLSCs as c-kit+/CD4−/CD8− cells and found that they have a similar gene expression profile as T cell progenitors. Additionally, we found that AP-1 gene family members, including
Junb, Jund, and Fosb, were up-regulated in the ATLSC fraction. The results of an in vitro assay showed that ATLSCs cultured with cytokines known to promote stem
cell expansion, such as stem cell factor (SCF), showed highly proliferative activity and maintained their stem cell fraction. Inhibition of c-kit–SCF signaling with the
neutralizing antibody ACK2 affected ATLSC self-renewal and proliferation. Experiments in Sl/Sld mice, which have a mutation in the membrane-bound c-kit ligand, found that ATL development was completely blocked in these mice. These results clearly suggest that the c-kit–SCF signal plays a key role in ATLSC self-renewal and in ATL initiation and disease progression.},
 pages = {51027--51043},
 title = {Impact of the SCF signaling pathway on leukemia stem cell mediated ATL initiation and progression in an HBZ transgenic mouse model},
 volume = {7},
 year = {2016}
}