title: A Possible Role for WNT5A Hypermethylation in Pediatric Acute Lymphoblastic Leukemia.
abstract: OBJECTIVE
  WNT5A is one of the most studied noncanonical WNT ligands and is shown to be deregulated in different tumor types. Our aim was to clarify whether hypermethylation might be the cause of low WNT5A mRNA levels and whether we could restore this downregulation by reversing the event.
  
  
  METHODS
  The expression of WNT5A mRNA was studied in a large acute lymphoblastic leukemia (ALL) patient group (n=86) by quantitative real-time PCR. The methylation status was detected by methylation-specific PCR (MSPCR) and bisulphate sequencing. In order to determine whether methylation has a direct effect on WNT5A expression, disease-representative cell lines were treated by 5'-aza-20-deoxycytidine.
  
  
  RESULTS
  Here we designed a validation experiment of the WNT5A gene, which was previously examined and found to be differentially expressed by microarray study in 31 T-cell ALL patients. The expression levels were confirmed by quantitative real-time PCR and the expression levels were significantly lower in T-cell ALL patients than in control thymic subsets (p=0.007). MSPCR revealed that 86% of the patients were hypermethylated in the WNT5A promoter region. Jurkat and RPMI cell lines were treated with 5'-aza-20-deoxycytidine and WNT5A mRNA expression was restored after treatment.
  
  
  CONCLUSIONS
  According to our results, WNT5A hypermethylation does occur in ALL patients and it has a direct effect on mRNA expression. Our findings show that epigenetic changes of WNT signaling can play a role in ALL pathogenesis and reversing methylation might be useful as a possible treatment of leukemia.
authors: Özden
authors: Ö
authors: Hatırnaz Ng
authors: Sinem
authors: S
authors: Fırtına
authors: İsmail
authors: İ
authors: Can
authors: Zeynep
authors: Z
authors: Karakaş
authors: Leyla
authors: L
authors: Ağaoğlu
authors: Ömer
authors: Ö
authors: Doğru
authors: Tiraje
authors: T
authors: Celkan
authors: Arzu
authors: A
authors: Akçay
authors: Yıldız
authors: Y
authors: Yıldırmak
authors: Çetin
authors: Ç
authors: Timur
authors: Uğur
authors: U
authors: Özbek
authors: İstanbul University Faculty of Medicine, Institute of Experimental Medicine Research (DETAE), Department of Genetics, İstanbul, Turkey Phone: +90 212 414 20 00-33312 E-mail: mugeay@istanbul.edu.tr.
authors: Müge
authors: M
authors: Sayitoğlu
mesh_terms: D000293:Adolescent; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019169:Jurkat Cells; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D060449:Wnt Signaling Pathway / Q000502:physiology; D000071818:Wnt-5a Protein / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C085389:WNT5A protein, human; D000071818:Wnt-5a Protein; D000077209:Decitabine; D001374:Azacitidine