title: Restored expression of vitamin D receptor and sensitivity to 1,25-dihydroxyvitamin D3 in response to disrupted fusion FOP2-FGFR1 gene in acute myeloid leukemia cells.
abstract: BACKGROUND
  Acute myeloid leukemia (AML) cells can be induced to undergo terminal differentiation with subsequent loss of tumorigenicity using 1,25-dihydroxyvitamin D3 (1,25D) alone or in combination with hematopoietic cytokines. KG1 cells are resistant to 1,25D-induced cell differentiation. These cells have the aberrant signal transduction resulting from a constitutively active fusion protein FOP2-FGFR1, a constitutively active STAT1 and a high level of interferon (IFN) stimulated genes (ISGs).
  
  
  METHODS
  In this paper we report that in KG1 cells with constitutively activated protein FOP2-FGFR1 delivery of plasmid DNA disrupted FOP2-FGFR1 fusion gene.
  
  
  RESULTS
  As a consequence, STAT1 signal transduction pathway became switched off, the expression of vitamin D receptor (VDR) gene was increased and sensitivity to 1,25D-induced differentiation was restored. The activation of ISGs in KG1 cells resulted in resistance to externally added IFNs, and also this effect was reversed in cells with disrupted FOP2-FGFR1 fusion gene.
  
  
  CONCLUSIONS
  In this paper we have documented for the first time a link between constitutively active STAT1 signal transduction pathway, high level of ISGs and low expression of VDR gene.
  
  
  CONCLUSIONS
  We show in this paper that delivery of plasmid DNA to the cells may disrupt fusion gene FOP2-FGFR1 which occurs in a disease entity called 8p11 myeloproliferative syndrome. Inhibition of the FOP2-FGFR1 signal transduction pathway restored sensitivity of the cells to 1,25D-induced cell differentiation.
authors.affiliation: Laboratory of Protein Biochemistry, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383 Wroclaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Marchwicka
authors.affiliation: Laboratory of Protein Biochemistry, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383 Wroclaw, Poland.
authors.forename: Aoife
authors.initials: A
authors.lastname: Corcoran
authors.affiliation: Laboratory of Protein Biochemistry, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383 Wroclaw, Poland.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Berkowska
authors.affiliation: Laboratory of Protein Biochemistry, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383 Wroclaw, Poland.
authors.forename: Ewa
authors.identifier: 0000-0002-6808-5464
authors.initials: E
authors.lastname: Marcinkowska
keywords: DNA delivery; Differentiation; Fusion protein; Interferon signaling; Leukemia; Transcription factor; Vitamin D receptor
references.citation: Nucleic Acids Res. 2010 Nov;38(20):6985-96
references.pmid: 20587502
references.citation: Mol Psychiatry. 2008 Mar;13(3):293-301
references.pmid: 17486106
references.citation: Nat Cell Biol. 2003 Sep;5(9):834-9
references.pmid: 12942087
references.citation: Nat Rev Immunol. 2014 Jan;14(1):36-49
references.pmid: 24362405
references.citation: Endocrinology. 2000 Aug;141(8):2829-36
references.pmid: 10919269
references.citation: Clin Microbiol Rev. 2001 Oct;14(4):778-809, table of contents
references.pmid: 11585785
references.citation: J Nutr. 1996 Apr;126(4 Suppl):1159S-64S
references.pmid: 8642450
references.citation: Steroids. 2008 Dec 22;73(14):1359-66
references.pmid: 18644400
references.citation: FEBS Lett. 2007 May 1;581(9):1751-7
references.pmid: 17418144
references.citation: J Clin Invest. 1986 Aug;78(2):424-30
references.pmid: 3461004
references.citation: Curr Opin Cell Biol. 1995 Oct;7(5):690-6
references.pmid: 8573344
references.citation: Eur J Biochem. 1986 Feb 17;155(1):11-7
references.pmid: 3753936
references.citation: J Cell Biochem. 2015 Aug;116(8):1500-12
references.pmid: 25694395
references.citation: Leukemia. 2002 Aug;16(8):1484-9
references.pmid: 12145689
references.citation: PLoS One. 2014 Mar 18;9(3):e91752
references.pmid: 24642534
references.citation: Nat Rev Cancer. 2003 Feb;3(2):89-101
references.pmid: 12563308
references.citation: Blood. 1989 Jan;73(1):284-9
references.pmid: 2462937
references.citation: Biomed Res Int. 2014;2014:817024
references.pmid: 25254215
references.citation: Hematol Oncol. 2010 Dec;28(4):185-91
references.pmid: 20301229
references.citation: Trends Immunol. 2002 Jun;23(6):301-4
references.pmid: 12072369
references.citation: Mol Endocrinol. 2010 Jan;24(1):128-47
references.pmid: 19897601
references.citation: J Clin Invest. 2002 Apr;109(8):1091-9
references.pmid: 11956247
references.citation: Mol Aspects Med. 2015 Feb;41:1-115
references.pmid: 25543955
references.citation: J Biol Chem. 1986 Jul 5;261(19):8811-6
references.pmid: 3087979
references.citation: Blood. 2006 Dec 15;108(13):4202-4
references.pmid: 16946300
references.citation: Genes Chromosomes Cancer. 2001 Oct;32(2):155-63
references.pmid: 11550283
references.citation: Mol Ther. 2005 Jan;11(1):112-9
references.pmid: 15585412
references.citation: Crit Rev Clin Lab Sci. 2005;42(5-6):473-514
references.pmid: 16390682
references.citation: PLoS One. 2013 Jul 29;8(7):e71042
references.pmid: 23923049
references.citation: J Steroid Biochem Mol Biol. 2011 Aug;126(1-2):46-54
references.pmid: 21550403
references.citation: Nat Rev Immunol. 2008 Jul;8(7):559-68
references.pmid: 18575461
references.citation: J Virol. 1992 Apr;66(4):2564-9
references.pmid: 1548781
references.citation: J Steroid Biochem Mol Biol. 2012 Nov;132(3-5):220-6
references.pmid: 22789609
references.citation: J Interferon Cytokine Res. 2011 Jan;31(1):49-57
references.pmid: 21190483
references.citation: Cell Signal. 2011 Nov;23(11):1758-66
references.pmid: 21745565
references.citation: Leuk Res. 2010 May;34(5):649-57
references.pmid: 19880182
references.citation: N Engl J Med. 2013 Jul 11;369(2):111-21
references.pmid: 23841729