C/EBPb is a critical mediator of IFN-a–induced exhaustion of chronic myeloid leukemia stem cells

Asumi Yokota, Hideyo Hirai, Ryuichi Sato, Hiroko Adachi, Fumiko Sato, Yoshihiro Hayashi, Atsushi Sato, Naoka Kamio, Yasuo Miura, Masakazu Nakano, Daniel G. Tenen, Shinya Kimura, Kei Tashiro, Taira Maekawa

研究成果: Article査読

3 被引用数 (Scopus)

抄録

Even in the era of ABL tyrosine kinase inhibitors, eradication of chronic myeloid leukemia (CML) stem cells is necessary for complete cure of the disease. Interferon-a (IFN-a) has long been used for the treatment of chronic-phase CML, but its mechanisms of action against CML stem cells remain unclear. We found that IFN-a upregulated CCAAT/enhancer binding protein b (C/EBPb) in BCR-ABL–expressing mouse cells by activating STAT1 and STAT5, which were recruited to a newly identified 39 distal enhancer of Cebpb that contains tandemly aligned IFN-g–activated site elements. Suppression or deletion of the IFN-g–activated site elements abrogated IFN-a–dependent upregulation of C/EBPb. IFN-a induced differentiation and exhaustion of CML stem cells, both in vitro and in vivo, in a C/EBPb-dependent manner. In addition, IFN-a upregulated C/EBPb and induced exhaustion of lineage2 CD341 cells from CML patients. Collectively, these results clearly indicate that C/EBPb is a critical mediator of IFN-a–induced differentiation and exhaustion of CML stem cells.

本文言語English
ページ(範囲)476-488
ページ数13
ジャーナルBlood Advances
3
3
DOI
出版ステータスPublished - 12-02-2019

All Science Journal Classification (ASJC) codes

  • Hematology

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