title: Protein tyrosine phosphatases receptor type D is a potential tumour suppressor gene inactivated by deoxyribonucleic acid methylation in paediatric acute myeloid leukaemia.
abstract: OBJECTIVE
  Protein tyrosine phosphatases receptor type D (PTPRD) is a tumour suppressor gene, and its epigenetic silencing is frequently found in glioblastoma. As aberrant deoxyribonucleic acid (DNA) methylation patterning has been shown to play a role in leukaemogenesis, we studied the promoter methylation, expression profiles and molecular functions of PTPRD in paediatric patients with acute myeloid leukaemia (AML).
  
  
  METHODS
  Bone marrow specimens were obtained from 32 Chinese patients with a mean age of 7.2 years (range 1.1-16.5). PTPRD and methylation status were evaluated by real-time polymerase chain reaction (PCR) and methylation-specific PCR. Western blot and flow cytometry techniques were also used.
  
  
  RESULTS
  PTPRD expression was decreased by promoter region methylation in six AML cells and methylated in 21 (65.6%) of the 32 samples. In addition, PTPRD expression could be induced by the DNA demethylating agent 5-aza-2'-deoxycytidine. Furthermore, functional studies showed that overexpression of PTPRD in AML cells inhibited cell proliferation and clonogenicity as well as inducing apoptosis. However, PTPRD knockdown increased cell proliferation. These effects were associated with downregulation of cyclin D1, c-myc and upregulation of Bax.
  
  
  CONCLUSIONS
  The results of this study demonstrated that PTPRD was a potential tumour suppressor gene inactivated by DNA methylation in paediatric AML.
authors.affiliation: Department of Paediatrics, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Gastroenterology, Nantong Third People's Hospital, Nantong, Jiangsu, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Nantong Third People's Hospital, Nantong, Jiangsu, China.
authors.forename: Ju-Hua
authors.initials: JH
authors.lastname: Ji
authors.affiliation: Department of Gastroenterology, Nantong Third People's Hospital, Nantong, Jiangsu, China.
authors.forename: Tai-Feng
authors.initials: TF
authors.lastname: Shi
authors.affiliation: School of Medicine, Nantong University, Nantong, Jiangsu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors.forename: Chun-Qiu
authors.initials: CQ
authors.lastname: Xia
mesh_terms: D000293:Adolescent; D017209:Apoptosis; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D018922:HL-60 Cells; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology* / Q000235:genetics; D008297:Male; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics*; D020298:U937 Cells
chemical_list: C090899:PTPRD protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
keywords: Acute myeloid leukaemia; Cell proliferation; Deoxyribonucleic acid methylation; Protein tyrosine phosphatases receptor type D; Tumour suppressor gene