title: Dysregulation of the DKK1 gene in pediatric B-cell acute lymphoblastic leukemia.
abstract: The canonical Wingless-type (WNT) pathway is involved in normal hematopoietic cell development and deregulated WNT signaling is implicated in the development of hematological malignancies. Dickkopf 1 (DKK1) acts as a modulator of the β-catenin regulated canonical pathway. Activation of DKK1 leads to apoptosis and growth suppression, whereas silencing by promoter hypermethylation results in abnormal WNT activation. The secreted inhibitor Dickkopf can antagonize WNT signaling by competitively binding to low density lipoprotein receptors (LRPs) 5 and 6.
  
  
  
  We studied DKK1 gene promoter methylation and investigated DKK1, β-catenin, LRP5, and LRP6 mRNA levels in B-cell acute lymphoblastic leukemia (B-ALL) patients (n = 90). Methylation-specific PCR and bisulfite sequencing were used for methylation profiling and quantitative real-time PCR was used for mRNA detection.
  
  
  
  The DKK1 gene was examined for its promoter methylation and only 33% of patients were found methylated. On the other hand, B-ALL cases showed high expression of DKK1 (P = 0.01), LRP5 (P = 0.04), and LRP6 (P = 0.02) compared to normal bone marrow cells.
  
  
  
  DKK1 methylation exists in some of cases but is not sufficient for WNT pathway activation alone in pediatric B-ALL.
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, İstanbul University, İstanbul, Turkey.
authors.forename: Sinem
authors.initials: S
authors.lastname: Firtina
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, İstanbul University, İstanbul, Turkey.
authors.forename: Özden
authors.initials: Ö
authors.lastname: Hatirnaz Ng
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, İstanbul University, İstanbul, Turkey.
authors.forename: Yücel
authors.initials: Y
authors.lastname: Erbilgin
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, İstanbul University, İstanbul, Turkey.
authors.forename: Uğur
authors.initials: U
authors.lastname: Özbek
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, İstanbul University, İstanbul, Turkey.
authors.forename: Müge
authors.initials: M
authors.lastname: Sayitoğlu
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D011973:Receptors, LDL / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000032:analysis / Q000235:genetics / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D011973:Receptors, LDL; D051176:beta Catenin