title: Epigenetic regulation of PAX5 expression in acute T-cell lymphoblastic leukemia.
abstract: The analysis of genomic alterations in acute lymphoblastic leukemia (ALL) has provided new insights for prognosis and possible targets of novel therapies. In T-ALL the role of molecular abnormalities has still to be determined. Deregulated promoter hypermethylation of critical genes like PAX5 may have a significant impact on the course of ALL. Samples derived from 75 patients with ALL (B-ALL = 24, T-ALL = 51) and from healthy volunteers were analyzed. PAX5 expression was assessed by micro-array analysis (HG-U133plus 2.0) and correlated with promoter CpG island methylation of PAX5 using a pyrosequencing approach. The analyzed CpG marks in the promoter region of PAX5 were completely and uniformly unmethylated in the control group of healthy individuals. The T-ALL cases featured even higher methylation levels (median: 20%) with a strong variation of values of up to 85% methylation. Analysis of the association of altered methylation levels with gene expression data indicated a differential epigenetic regulation of PAX5 through promoter methylation which may contribute to the pathogenesis of this disease.
authors.affiliation: Institute of Transfusion Medicine and Immunology, University Heidelberg, Friedrich-Ebert-Straße 107, 68167 Mannheim, Germany. gero.huetter@medma.uni-heidelberg.de
authors.forename: Gero
authors.initials: G
authors.lastname: Hütter
authors.forename: Martin
authors.initials: M
authors.lastname: Kaiser
authors.forename: Martin
authors.initials: M
authors.lastname: Neumann
authors.forename: Maximilian
authors.initials: M
authors.lastname: Mossner
authors.forename: Daniel
authors.initials: D
authors.lastname: Nowak
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Baldus
authors.forename: Nicola
authors.initials: N
authors.lastname: Gökbuget
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D051757:PAX5 Transcription Factor / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D055815:Young Adult
chemical_list: D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human