TGF-β–FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia

Kazuhito Naka (), Takayuki Hoshii, Teruyuki Muraguchi, Yuko Tadokoro, Takako Ooshio, Yukio Kondo, Shinji Nakao, Noboru Motoyama and Atsushi Hirao ()
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Kazuhito Naka: Center for Cancer and Stem Cell Research, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-0934, Japan
Takayuki Hoshii: Center for Cancer and Stem Cell Research, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-0934, Japan
Teruyuki Muraguchi: Center for Cancer and Stem Cell Research, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-0934, Japan
Yuko Tadokoro: Center for Cancer and Stem Cell Research, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-0934, Japan
Takako Ooshio: Center for Cancer and Stem Cell Research, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-0934, Japan
Yukio Kondo: Cellular Transplantation Biology, Kanazawa University, Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan
Shinji Nakao: Cellular Transplantation Biology, Kanazawa University, Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan
Noboru Motoyama: National Institute for Longevity Sciences, National Center for Gerontology and Geriatrics, Obu, Aichi 474-8522, Japan
Atsushi Hirao: Center for Cancer and Stem Cell Research, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-0934, Japan

Nature, 2010, vol. 463, issue 7281, 676-680

Abstract: Leukaemia recurrence Chronic myeloid leukaemia (CML) is caused by a BCR-ABL fusion that generates a constitutively active tyrosine kinase. Although inhibition of tyrosine kinase with imatinib has been used successfully for CML therapy, it does not deplete the leukaemia-initiating cells (LICs) that drive the recurrence of CML. Naka et al. show that Foxo3a plays an essential role in the maintenance of LICs in CML, and that TGF-β is a critical regulator of Akt activation in LICs and controls Foxo3a localization. They also show that treatment of LICs in human CML with a TGF-β inhibitor impairs their colony-forming ability in vitro.

Date: 2010
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DOI: 10.1038/nature08734

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