title: Hypomethylation of the CTGF gene locus is a common feature of paediatric pre-B acute lymphoblastic leukaemia.
abstract: The connective tissue growth factor gene (CTGF) is aberrantly expressed in 75% of precursor B-cell acute lymphoblastic leukaemias (pre-B ALL) and is associated with poor outcome. We identified consistent hypomethylation of the CTGF locus in primary pre-B ALL specimens regardless of CTGF expression. By contrast, primary T-cell ALL specimens, which do not express CTGF, exhibited distinctive patterns of hypermethylation. Furthermore, we confirmed that global changes in DNA methylation and histone acetylation can both functionally modulate CTGF expression in pre-B ALL cell lines. These data suggest that hypomethylation of the CTGF locus is an essential prerequisite for aberrant CTGF expression in pre-B ALL.
authors.affiliation: Division of Children's Leukaemia and Cancer Research, Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, WA, Australia.
authors.forename: Mathew D
authors.initials: MD
authors.lastname: Welch
authors.forename: Wayne K
authors.initials: WK
authors.lastname: Greene
authors.forename: Ursula R
authors.initials: UR
authors.lastname: Kees
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002648:Child; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D000077209:Decitabine; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: C526317:CCN2 protein, human; D006877:Hydroxamic Acids; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D055513:Connective Tissue Growth Factor; C012589:trichostatin A; D000077209:Decitabine; D001374:Azacitidine
keywords: DNA methylation; Leukaemia; bisulfite sequencing; pre-B ALL