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Title: All-trans retinoic acid combined with 5-Aza-2 Prime -deoxycitidine induces C/EBP{alpha} expression and growth inhibition in MLL-AF9-positive leukemic cells

Abstract

Highlights: Black-Right-Pointing-Pointer We tested whether ATRA and 5-Aza affect AML cell differentiation and growth. Black-Right-Pointing-Pointer Cell differentiation and growth arrest were induced in MLL-AF9-expressing cells. Black-Right-Pointing-Pointer Increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1 were also observed. Black-Right-Pointing-Pointer MLL-AF4/AF5q31-expressing cells are less sensitive to ATRA and 5-Aza. Black-Right-Pointing-Pointer Different MLL fusion has distinct epigenetic properties related to RA pathway. -- Abstract: The present study tested whether all-trans retinoic acid (ATRA) and 5-Aza-2 Prime -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.

Authors:
 [1];  [1]; ; ; ; ; ; ;  [1];  [2];  [1]
  1. Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan)
  2. Department of Pediatrics, University of Yamanashi, Yamanashi (Japan)
Publication Date:
OSTI Identifier:
22210329
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 428; Journal Issue: 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL DIFFERENTIATION; DEOXYCYTIDINE; IN VITRO; INACTIVATION; INHIBITION; MYELOID LEUKEMIA; PROTEINS; RETINOIC ACID

Citation Formats

Fujiki, Atsushi, Imamura, Toshihiko, E-mail: imamura@koto.kpu-m.ac.jp, Sakamoto, Kenichi, Kawashima, Sachiko, Yoshida, Hideki, Hirashima, Yoshifumi, Miyachi, Mitsuru, Yagyu, Shigeki, Nakatani, Takuya, Sugita, Kanji, and Hosoi, Hajime. All-trans retinoic acid combined with 5-Aza-2 Prime -deoxycitidine induces C/EBP{alpha} expression and growth inhibition in MLL-AF9-positive leukemic cells. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.09.131.
Fujiki, Atsushi, Imamura, Toshihiko, E-mail: imamura@koto.kpu-m.ac.jp, Sakamoto, Kenichi, Kawashima, Sachiko, Yoshida, Hideki, Hirashima, Yoshifumi, Miyachi, Mitsuru, Yagyu, Shigeki, Nakatani, Takuya, Sugita, Kanji, & Hosoi, Hajime. All-trans retinoic acid combined with 5-Aza-2 Prime -deoxycitidine induces C/EBP{alpha} expression and growth inhibition in MLL-AF9-positive leukemic cells. United States. doi:10.1016/J.BBRC.2012.09.131.
Fujiki, Atsushi, Imamura, Toshihiko, E-mail: imamura@koto.kpu-m.ac.jp, Sakamoto, Kenichi, Kawashima, Sachiko, Yoshida, Hideki, Hirashima, Yoshifumi, Miyachi, Mitsuru, Yagyu, Shigeki, Nakatani, Takuya, Sugita, Kanji, and Hosoi, Hajime. Fri . "All-trans retinoic acid combined with 5-Aza-2 Prime -deoxycitidine induces C/EBP{alpha} expression and growth inhibition in MLL-AF9-positive leukemic cells". United States. doi:10.1016/J.BBRC.2012.09.131.
@article{osti_22210329,
title = {All-trans retinoic acid combined with 5-Aza-2 Prime -deoxycitidine induces C/EBP{alpha} expression and growth inhibition in MLL-AF9-positive leukemic cells},
author = {Fujiki, Atsushi and Imamura, Toshihiko, E-mail: imamura@koto.kpu-m.ac.jp and Sakamoto, Kenichi and Kawashima, Sachiko and Yoshida, Hideki and Hirashima, Yoshifumi and Miyachi, Mitsuru and Yagyu, Shigeki and Nakatani, Takuya and Sugita, Kanji and Hosoi, Hajime},
abstractNote = {Highlights: Black-Right-Pointing-Pointer We tested whether ATRA and 5-Aza affect AML cell differentiation and growth. Black-Right-Pointing-Pointer Cell differentiation and growth arrest were induced in MLL-AF9-expressing cells. Black-Right-Pointing-Pointer Increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1 were also observed. Black-Right-Pointing-Pointer MLL-AF4/AF5q31-expressing cells are less sensitive to ATRA and 5-Aza. Black-Right-Pointing-Pointer Different MLL fusion has distinct epigenetic properties related to RA pathway. -- Abstract: The present study tested whether all-trans retinoic acid (ATRA) and 5-Aza-2 Prime -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.},
doi = {10.1016/J.BBRC.2012.09.131},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 428,
place = {United States},
year = {2012},
month = {11}
}