title: Hypermethylation of two CpG sites upstream of CASP8AP2 promoter influences gene expression and treatment outcome in childhood acute lymphoblastic leukemia.
abstract: DNA hypermethylation of Caspase 8 associated protein 2 (CASP8AP2) and its role in childhood acute lymphoblastic leukemia (ALL) is unclear. We analyzed methylation status of CpG sites upstream of CASP8AP2 gene in 86 children with ALL by bisulfite sequencing and quantitative PCR. Methylation percentage of two CpG sites at positions of -1189 and -1176 was inversely correlated with mRNA expression (Spearman correlation: -0.333, P=0.002). High methylation was associated with the existence of minimal residual disease (MRD) at day 78 (P=0.035), The patients in high methylation group had a poor treatment outcome. The combination of methylation level and MRD at day 33 might improve current risk stratification.
authors: Key Laboratory of Major Diseases in Children (Capital Medical University), Ministry of Education; Hematology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors: Zhi-Gang
authors: ZG
authors: Li
authors: Ying
authors: Y
authors: Jiao
authors: Wei-Jing
authors: WJ
authors: Li
authors: Guo-Ren
authors: GR
authors: Deng
authors: Lei
authors: L
authors: Cui
authors: Chao
authors: C
authors: Gao
authors: Xiao-Xi
authors: XX
authors: Zhao
authors: Min-Yuan
authors: MY
authors: Wu
authors: Hong-Ti
authors: HT
authors: Jia
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C485604:CASP8AP2 protein, human; D002135:Calcium-Binding Proteins; D012333:RNA, Messenger
keywords: Acute lymphoblastic leukemia; CASP8AP2; Childhood; Methylation; Prognosis