title: Gravin gene expression in acute myeloid leukemia.
abstract: Acute leukemias are caused by genetic and epigenetic mechanisms involving tumor suppressor genes and oncogenes. Aberrant DNA methylation patterns are the most frequent molecular alterations detected in acute myeloid leukemia (AML). Gravin is down-regulated in several solid tumors and is implicated in tumorigenesis. To explore its role in the molecular pathogenesis and its possible prognostic importance in AML, we have evaluated the expression levels of the gravin gene in 83 acute myeloid leukemia patients as compared with controls using quantitative real-time polymerase chain reaction (qRT-PCR). Mean gravin expression was 0.53 ± 1.34 and 8.81 ± 11.6 for patients and controls, respectively, and was found to be about 16-fold lower than controls. Gravin gene expression was lower than controls in 83.1 % (69/83) and was similar to controls in 16.9 % (14/83) of cases (p < 0.0001). It was found that there was no significant correlation between gravin expression and laboratory prognostic markers (p > 0.05). Gravin expression was highest in complete remission (1.065 ± 1.79) and lowest in relapse (0.019 ± 0.03) with a statistical difference (p = 0.004). Patients with gravin expression below median level had higher risk to develop relapse (OR = 8.689, 95 % CI = 2.464-30.638; p < 0.0001). No statistical correlation was reported between gravin expression and survival times (OS, DFS) (p = 0.482, 0.409, respectively), and this was confirmed in multivariate analysis. Gravin gene expression was found to be decreased in acute myeloid leukemia, and the degree of its decreased expression has been found to be correlated with poor prognosis.
authors.affiliation: Physical Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt.
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Mostafa
authors.forename: Raida S
authors.initials: RS
authors.lastname: Yahia
authors.forename: Hanaa M
authors.initials: HM
authors.lastname: Abd El Messih
authors.forename: Eman
authors.initials: E
authors.lastname: El-Sisy
authors.forename: Doaa M
authors.initials: DM
authors.lastname: El Ghannam
mesh_terms: D054758:A Kinase Anchor Proteins / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins
references.citation: Br J Haematol. 2004 Aug;126(4):508-11
references.pmid: 15287943
references.citation: Biochem Biophys Res Commun. 1995 Jan 26;206(3):916-26
references.pmid: 7832805
references.citation: Leukemia. 2004 Jan;18(1):120-5
references.pmid: 14586477
references.citation: Trends Mol Med. 2004 Apr;10(4):158-62
references.pmid: 15059606
references.citation: Oncol Rep. 2004 Jul;12(1):97-9
references.pmid: 15201966
references.citation: Leukemia. 2006 Jun;20(6):1080-8
references.pmid: 16617321
references.citation: Leuk Lymphoma. 2007 Jun;48(6):1167-72
references.pmid: 17577780
references.citation: Cancer Res. 2007 Feb 1;67(3):1370-7
references.pmid: 17283175
references.citation: Curr Drug Targets. 2007 Jun;8(6):715-25
references.pmid: 17584027
references.citation: Front Biosci. 2002 Aug 01;7:d1782-97
references.pmid: 12133808
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Biochem Biophys Res Commun. 2002 Oct 11;297(5):1112-20
references.pmid: 12372401
references.citation: Oncogene. 2002 Aug 22;21(37):5804-13
references.pmid: 12173052
references.citation: Biochem J. 2004 Apr 1;379(Pt 1):1-9
references.pmid: 14715081
references.citation: Cancer Res. 2001 Jul 15;61(14):5644-51
references.pmid: 11454719
references.citation: Leukemia. 2005 Jul;19(7):1216-23
references.pmid: 15858619
references.citation: J Cell Sci. 2001 Apr;114(Pt 8):1431-7
references.pmid: 11282019
references.citation: Nature. 2000 Aug 17;406(6797):747-52
references.pmid: 10963602
references.citation: Clin Lab Haematol. 2002 Feb;24(1):1-13
references.pmid: 11843892
references.citation: Oncogene. 2004 Sep 16;23(42):7095-103
references.pmid: 15258566
references.citation: Mol Cell Biol. 1995 May;15(5):2754-62
references.pmid: 7739556
references.citation: Cancer. 2003 May 1;97(9):2229-35
references.pmid: 12712476
references.citation: Ann N Y Acad Sci. 2003 Mar;983:71-83
references.pmid: 12724213
references.citation: Gastroenterology. 2006 Sep;131(3):797-808
references.pmid: 16952549
references.citation: Technol Cancer Res Treat. 2006 Dec;5(6):565-71
references.pmid: 17121432
references.citation: Clin Cancer Res. 2003 Jan;9(1):68-75
references.pmid: 12538453
references.citation: J Vasc Res. 2001 Mar-Apr;38(2):163-75
references.pmid: 11316952
references.citation: Oncogene. 2004 May 6;23(21):3737-48
references.pmid: 14990994
references.citation: Curr Biol. 1997 Jan 1;7(1):52-62
references.pmid: 9000000
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1176-81
references.pmid: 11158614
references.citation: J Mol Signal. 2011 Aug 10;6:8
references.pmid: 21831305