Bi-allelic silencing of the Fanconi anaemia gene FANCF in acute myeloid leukaemia.
Fanconi anaemia (FA) is a chromosomal instability disorder associated with a high risk of acute myeloid leukaemia (AML). Previous work has shown that the AML cell line CHRF-288, derived from a sporadic AML-M7 patient, does not express FANCF protein and exhibits a cellular FA phenotype. We show that this phenotype is corrected by a FANCF-expressing plasmid and that the absence of FANCF protein is explained by hypermethylation of the promoter region of the FANCF gene. As FANCF is localized in a hot-spot region for somatic hypermethylation (11p15), FANCF silencing might be an early step in sporadic carcinogenesis, including leukaemogenesis.
Tischkowitz
Marc
M
Department of Medical and Molecular Genetics, Division of Genetics and Development Guy's, King's and St Thomas's School of Medicine, King's College London, Guy's Hospital, London, UK.
Ameziane
Najim
N
Waisfisz
Quinten
Q
De Winter
Johan P
JP
Harris
Richard
R
Taniguchi
Toshiyasu
T
D'Andrea
Alan
A
Hodgson
Shirley V
SV
Mathew
Christopher G
CG
Joenje
Hans
H
D000208:Acute Disease; D000483:Alleles; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005199:Fanconi Anemia / Q000235:genetics; D052219:Fanconi Anemia Complementation Group F Protein; D020868:Gene Silencing; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*
C499901:FANCF protein, human; D052219:Fanconi Anemia Complementation Group F Protein; D016601:RNA-Binding Proteins