All-trans retinoic acid combined with 5-Aza-2 %26apos;-deoxycitidine induces C/EBP alpha expression and growth inhibition in MLL-AF9-positive leukemic cells

作者：Fujiki Atsushi; Imamura Toshihiko^*; Sakamoto Kenichi; Kawashima Sachiko; Yoshida Hideki; Hirashima Yoshifumi; Miyachi Mitsuru; Yagyu Shigeki; Nakatani Takuya; Sugita Kanji; Hosoi Hajime

来源：Biochemical and Biophysical Research Communications, 2012, 428(2): 216-223.

DOI：10.1016/j.bbrc.2012.09.131

• Acute myeloid leukemia
• MLL rearrangement
• CCAAT/enhancer binding protein alpha
• All-trans retinoic acid
• 5-Aza-2 %26apos
• -deoxycytidine
• Retinoic acid pathway

The present study tested whether all-trans retinoic acid (ATRA) and 5-Aza-2%26apos;-deoxycitidine (5-Aza) affect AML cell differentiation and growth in vitro by acting on the CCAAT/enhancer binding protein alpha (C/EBP alpha) and c-Myc axis. After exposure to a combination of these agents, cell differentiation and growth arrest were significantly higher in human and murine MLL-AF9-expressing cells than in MLL-AF4/AF5q31-expressing cells, which were partly associated with increased expression of C/EBP alpha, C/EBP epsilon, and PU.1, and decreased expression of c-Myc. These findings indicate that MLL-AF9-expressing cells are more sensitive to ATRA and 5-Aza, indicating that different MLL fusion proteins possess different epigenetic properties associated with retinoic acid pathway inactivation.

• 出版日期2012-11-16