Post-transcriptional modulation of C/EBPα prompts monocytic differentiation and apoptosis in acute myelomonocytic leukaemia cells

Yoshida, Hideki; Imamura, Toshihiko; Fujiki, Atsushi; Hirashima, Yoshifumi; Miyachi, Mitsuru; Inukai, Takeshi; Hosoi, Hajime

doi:10.1016/j.leukres.2012.01.009

« Previous Next »Leukemia Research
Volume 36, Issue 6 , Pages 735-741, June 2012

Post-transcriptional modulation of C/EBPα prompts monocytic differentiation and apoptosis in acute myelomonocytic leukaemia cells

Hideki Yoshida
- Department of Paediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Toshihiko Imamura
- Department of Paediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Corresponding author at: Department of Paediatrics, Kyoto Prefectural University of Medicine, Kajii-cho Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Tel.: +81 75 251 5571; fax: +81 75 252 1399.
Atsushi Fujiki
- Department of Paediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Yoshifumi Hirashima
- Department of Paediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Mitsuru Miyachi
- Department of Paediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Takeshi Inukai
- Department of Paediatrics, University of Yamanashi, Yamanashi, Japan
Hajime Hosoi
- Department of Paediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

Received 20 November 2011; received in revised form 8 January 2012; accepted 11 January 2012. published online 20 February 2012.

Abstract

CCAAT/enhancer binding protein alpha (C/EBPα) induction induces monocytic differentiation even in acute myeloid leukaemia (AML). In this study, the induction/activation of C/EBPα in myelomonocytic AML was investigated using a combination of all-trans retinoic acid (ATRA) and RAD001 (Everolimus), a mammalian target of rapamycin complex 1 (mTORC1) inhibitor. Combining these agents increased PU.1, C/EBPɛ and C/EBPα expression, increased the p42/p30 C/EBPα ratio, and decreased C/EBPα phosphorylation at serine 21, and was accompanied by growth inhibition, induction of CD11b expression and apoptosis in AML cell lines. Thus, agents that induce sufficient levels of C/EBPα expression might be useful in treating AML.

Keywords: Acute myeloid leukaemia, C/EBPα, RAD001, p42/p30 ratio, Dephosphorylation, mTOR, Apoptosis