title: Promoter methylation and expression levels of selected hematopoietic genes in pediatric B-cell acute lymphoblastic leukemia.
abstract: BACKGROUND
  Precursor B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common neoplasm in children and is characterized by genetic and epigenetic aberrations in hematopoietic transcription factor (TF) genes. This study evaluated promoter DNA methylation and aberrant expression levels of early- and late-acting hematopoietic TF genes homeobox A4 and A5 (HOXA4 and HOXA5), Meis homeobox 1 (MEIS1), T-cell acute lymphocytic leukemia 1 (TAL1), and interferon regulatory factors 4 and 8 (IRF4 and IRF8) in pediatric B-cell ALL.
  
  
  METHODS
  Blood samples of 38 ALL patients and 20 controls were obtained. DNA was treated with sodium bisulfite and DNA methylation level of HOXA4, HOXA5, MEIS1, TAL1, IRF4, and IRF8 was assessed using quantitative methylation-specific polymerase chain reaction (PCR). Relative gene expression was measured using quantitative reverse transcription-PCR.
  
  
  RESULTS
  Aberrant methylation of TAL1, IRF8, MEIS1, and IRF4 was observed in 26.3%, 7.9%, 5.3%, and 2.6% patients, respectively, but not in controls. HOXA4 and HOXA5 were methylated in some controls and hypermethylated in 16% and 5% patients, respectively. IRF8, MEIS1, and TAL1 expression was lower in patients than in controls. MEIS1 expression was inversely correlated with white blood cell (WBC) count. HOXA4 expression was down-regulated in patients with high risk according to the National Cancer Institute (NCI) classification. TAL1 methylation was slightly elevated in patients aged >9 years and in patients showing relapse, suggesting its potential prognostic value.
  
  
  CONCLUSIONS
  Aberrant methylation and expression of the selected hematopoietic genes were correlated with demographic/clinical prognostic factors of pediatric ALL, such as age, WBC count, and NCI risk classification.
authors.affiliation: Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Musialik
authors.affiliation: Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Bujko
authors.affiliation: Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Kober
authors.affiliation: Department of Pediatric Haematology & Oncology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wypych
authors.affiliation: Department of Pediatric Haematology & Oncology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Gawle-Krawczyk
authors.affiliation: Department of Pediatric Haematology & Oncology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Matysiak
authors.affiliation: Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Janusz Aleksander
authors.initials: JA
authors.lastname: Siedlecki
keywords: Acute lymphoblastic leukemia; DNA methylation; Gene expression; Transcription factors
references.citation: Zhonghua Yi Xue Za Zhi. 2013 Dec 24;93(48):3835-40
references.pmid: 24548444
references.citation: Best Pract Res Clin Haematol. 2011 Dec;24(4):489-503
references.pmid: 22127311
references.citation: Am J Hematol. 2011 Jan;86(1):2-11
references.pmid: 20981674
references.citation: Genes Dev. 2003 Jul 15;17(14):1703-8
references.pmid: 12832394
references.citation: Exp Hematol. 2004 Jan;32(1):11-24
references.pmid: 14725896
references.citation: Cancer Cell. 2002 Feb;1(1):75-87
references.pmid: 12086890
references.citation: Hum Mol Genet. 2009 Nov 1;18(21):4054-65
references.pmid: 19679565
references.citation: Methods. 2001 Dec;25(4):456-62
references.pmid: 11846615
references.citation: Leuk Lymphoma. 2004 Mar;45(3):567-74
references.pmid: 15160920
references.citation: Clin Cancer Res. 2007 Sep 1;13(17):5048-55
references.pmid: 17785556
references.citation: Leukemia. 2004 Jul;18(7):1231-7
references.pmid: 15103390
references.citation: Haematologica. 2010 Oct;95(10):1675-82
references.pmid: 20494936
references.citation: Leukemia. 2006 Jul;20(7):1326-9
references.pmid: 16688227
references.citation: PLoS One. 2013 Aug 15;8(8):e72326
references.pmid: 23977280
references.citation: J Immunol. 2007 Sep 15;179(6):3662-71
references.pmid: 17785802
references.citation: Epigenetics. 2012 Jun 1;7(6):535-41
references.pmid: 22531296
references.citation: PLoS One. 2011 Feb 28;6(2):e17012
references.pmid: 21386967
references.citation: Cancer Sci. 2008 Mar;99(3):467-78
references.pmid: 18190617
references.citation: Nucleic Acids Res. 2000 Apr 15;28(8):E32
references.pmid: 10734209
references.citation: Leukemia. 2011 Jul;25(7):1202-7
references.pmid: 21475251
references.citation: Oncogene. 2001 Feb 15;20(7):874-8
references.pmid: 11314021
references.citation: Blood. 1999 Jul 15;94(2):519-28
references.pmid: 10397719
references.citation: Genes Dev. 2007 Nov 15;21(22):2845-9
references.pmid: 18006680
references.citation: Mol Cell Biol. 1997 Nov;17(11):6448-58
references.pmid: 9343407
references.citation: Stem Cells Dev. 2012 Jan;21(1):133-42
references.pmid: 21749220
references.citation: Pediatr Blood Cancer. 2010 Dec 1;55(6):1072-82
references.pmid: 20672366
references.citation: Nature. 2007 Apr 12;446(7137):758-64
references.pmid: 17344859
references.citation: Oncogene. 2007 Oct 15;26(47):6766-76
references.pmid: 17934484
references.citation: Nucleic Acids Res. 2005 Dec 07;33(21):6895-905
references.pmid: 16396836
references.citation: Leukemia. 2003 Sep;17 (9):1845-50
references.pmid: 12970785