PMID- 23823656
OWN - NLM
STAT- MEDLINE
DCOM- 20140616
LR  - 20220218
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 28
IP  - 4
DP  - 2014 Apr
TI  - Induced differentiation of acute myeloid leukemia cells by activation of retinoid 
      X and liver X receptors.
PG  - 749-60
LID - 10.1038/leu.2013.202 [doi]
AB  - Use of all-trans retinoic acid (ATRA) as a differentiation agent has been limited 
      to acute promyelocytic leukemia (APL) as non-APL leukemias are insensitive to 
      ATRA. We recently demonstrated that the rexinoid, bexarotene, induces 
      differentiation and therapeutic responses in patients with refractory AML. 
      Rexinoids bind and activate retinoid X receptors (RXRs); however, rexinoids alone 
      are incapable of activating retinoic acid receptor (RAR)/RXR complexes, 
      suggesting that myeloid differentiation can occur independent of RAR. In this 
      study, we demonstrate that rexinoid differentiation of AML cells is RAR 
      independent and requires the expression of PU.1. Because of the promiscuousness 
      of RXR with other nuclear receptors, myeloid differentiation by bexarotene with 
      other nuclear receptor ligands was explored. Bexarotene cooperated with ATRA to 
      enhance differentiation in some AML cell lines; however, the combination of 
      bexarotene with the PPARgamma agonist rosiglitazone did not. In contrast, bexarotene 
      combined with liver X receptor (LXR) agonists, T0901317 or GW3965, induced potent 
      differentiation and cytotoxicity in AML cell lines and primary human AML cells, 
      but not in normal progenitor cells. These results suggest that RXR/LXR-regulated 
      gene expression in normal cells is deregulated in AML cells and identifies a 
      potential role for these agonists in differentiation therapy of non-APLs.
FAU - Sanchez, P V
AU  - Sanchez PV
AD  - Division of Hematology and Oncology, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia PA, USA.
FAU - Glantz, S T
AU  - Glantz ST
AD  - Division of Hematology and Oncology, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia PA, USA.
FAU - Scotland, S
AU  - Scotland S
AD  - Division of Hematology and Oncology, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia PA, USA.
FAU - Kasner, M T
AU  - Kasner MT
AD  - Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
FAU - Carroll, M
AU  - Carroll M
AD  - Division of Hematology and Oncology, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia PA, USA.
LA  - eng
GR  - K01 CA129151/CA/NCI NIH HHS/United States
GR  - R01 CA149566/CA/NCI NIH HHS/United States
GR  - K01-CA-129151/CA/NCI NIH HHS/United States
GR  - 1R01CA149566/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130704
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (CCAAT-Enhancer-Binding Protein-alpha)
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (Hydrocarbons, Fluorinated)
RN  - 0 (Liver X Receptors)
RN  - 0 (Nicotinic Acids)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Sulfonamides)
RN  - 0 (T0901317)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 0 (Trans-Activators)
RN  - 0 (proto-oncogene protein Spi-1)
RN  - 142805-41-2 (CEBPE protein, human)
RN  - 5688UTC01R (Tretinoin)
RN  - A61RXM4375 (Bexarotene)
RN  - UVU4X1103P (LG 100268)
SB  - IM
MH  - Bexarotene
MH  - CCAAT-Enhancer-Binding Protein-alpha/physiology
MH  - CCAAT-Enhancer-Binding Proteins/physiology
MH  - Cell Differentiation/drug effects
MH  - Cell Line, Tumor
MH  - Humans
MH  - Hydrocarbons, Fluorinated/pharmacology
MH  - Leukemia, Myeloid, Acute/*pathology
MH  - Liver X Receptors
MH  - Nicotinic Acids/pharmacology
MH  - Orphan Nuclear Receptors/*physiology
MH  - Proto-Oncogene Proteins/physiology
MH  - Retinoid X Receptors/*physiology
MH  - Sulfonamides/pharmacology
MH  - Tetrahydronaphthalenes/pharmacology
MH  - Trans-Activators/physiology
MH  - Tretinoin/pharmacology
PMC - PMC8835482
MID - NIHMS549959
COIS- Conflict of Interest: M.C. receives research support from Glaxo Smith Kline, 
      Sanofi Aventis Corporation and Tetralogic Pharmaceuticals.
EDAT- 2013/07/05 06:00
MHDA- 2014/06/17 06:00
PMCR- 2022/02/11
CRDT- 2013/07/05 06:00
PHST- 2012/06/14 00:00 [received]
PHST- 2013/06/20 00:00 [revised]
PHST- 2013/06/24 00:00 [accepted]
PHST- 2013/07/05 06:00 [entrez]
PHST- 2013/07/05 06:00 [pubmed]
PHST- 2014/06/17 06:00 [medline]
PHST- 2022/02/11 00:00 [pmc-release]
AID - leu2013202 [pii]
AID - 10.1038/leu.2013.202 [doi]
PST - ppublish
SO  - Leukemia. 2014 Apr;28(4):749-60. doi: 10.1038/leu.2013.202. Epub 2013 Jul 4.