title: Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among North Indian population.
abstract: Promoter hypermethylation mediates gene silencing in many neoplasms. Acute leukemia has been reported to harbor multiple genes aberrantly silenced by hypermethylation.
  
  
  OBJECTIVE
  In present study, we investigated the prevalence of hypermethylation of caspase-8 (CASP8), TMS1 and DAPK genes in correlation with clinicopathological factors in childhood acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  A case-control study has been conducted based on bone marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched healthy controls. Methylation specific polymerase chain reaction (PCR) and bisulfite sequencing PCR was performed to analyze the methylation status of these genes. Reverse transcription PCR and real time PCR was carried out to determine changes in the mRNA expression level of the genes due to hypermethylation.
  
  
  RESULTS
  Hypermethylation of the 5´CpG islands of the CASP8, TMS1 and DAPK gene promoters was found in 3.2, 6.4, and 13.6% of 125 childhood ALL samples from north Indian population, respectively. There were significant differences in pattern of hypermethylation of TMS1 (p = 0.045) and DAPK (p &lt; 0.001) between patients and healthy controls. Down-regulation of mRNA expression was found in cases in which CASP8, TMS1 and DAPK were hypermethylated.
  
  
  CONCLUSIONS
  The present study indicated the impact of hypermethylation-mediated inactivation of CASP8, TMS1 and DAPK genes, which is associated with risk of childhood ALL. This abnormality occurs in leukemogenesis and it may be used as a biomarker and for predicting the prognosis of ALL.
authors.affiliation: Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran 1411713131, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Nikbakht
authors.affiliation: Department of Biotechnology, IMS Engineering College, Ghaziabad (U.P.) 160012, India.
authors.forename: A K
authors.initials: AK
authors.lastname: Jha
authors.affiliation: Molecular Medicine Research Center (MMRC); Hormozgan University of Medical Science (HUMS); Bandar Abbass 7919915519, Iran.
authors.forename: K
authors.initials: K
authors.lastname: Malekzadeh
authors.affiliation: Department of Biotechnology, Panjab University, Chandigarh 160014, India.
authors.forename: M
authors.initials: M
authors.lastname: Askari
authors.affiliation: Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran 14176-13151, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Mohammadi
authors.affiliation: Advanced Pediatrics Center, PGIMER, Chandigarh 160014, India.
authors.forename: R K
authors.initials: RK
authors.lastname: Marwaha
authors.affiliation: Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh 160014, India.
authors.forename: D
authors.initials: D
authors.lastname: Kaul
authors.affiliation: Department of Biotechnology, Panjab University, Chandigarh 160014, India.
authors.forename: J
authors.initials: J
authors.lastname: Kaur
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D053468:CARD Signaling Adaptor Proteins; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; C402202:PYCARD protein, human; D012333:RNA, Messenger; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D053181:Caspase 8