title: Quantification of DAPK1 promoter methylation in bone marrow and peripheral blood as a follicular lymphoma biomarker.
abstract: Hypermethylation of DAPK1 promoter gene was found to be a frequent epigenetic alteration in follicular lymphoma (FL). We evaluated whether the quantification of DAPK1 methylation in the bone marrow (BM) and peripheral blood of FL patients at diagnosis and during follow-up provides important prognostic information. DAPK1 methylation was quantitated by real-time MethyLight PCR in 107 patients at diagnosis, at end of therapy, and during follow-up. Information on BCL2-IGH rearrangement and clinical characteristics were available for all patients. Aberrant DAPK1 methylation was found in 22 of 26 (85%) lymph node biopsy samples, 62 of 107 (58%) BM specimens, and 25 of 63 (40%) peripheral blood samples at diagnosis. DAPK1 methylation was greater in patients with BM infiltration and a higher Follicular Lymphoma International Prognostic Index score. The presence of aberrant DAPK1 methylation in BM significantly reduced progression-free survival following immunochemotherapy, independent of Follicular Lymphoma International Prognostic Index score. Residual or increased methylation after treatment was associated with an increased risk for relapse. With watchful waiting, greater DAPK1 methylation at diagnosis was associated with a shorter time to antilymphoma treatment. Our study indicates that quantification of DAPK1 methylation represents a prognostically relevant FL biomarker, with promising implications for risk assessment.
authors.affiliation: Institute of Hematology, Sacred Heart Catholic University of Rome, Rome, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Giachelia
authors.affiliation: Institute of Hematology, Sacred Heart Catholic University of Rome, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bozzoli
authors.affiliation: Institute of Hematology, Sacred Heart Catholic University of Rome, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: D'Alò
authors.affiliation: Institute of Hematology, Sacred Heart Catholic University of Rome, Rome, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Tisi
authors.affiliation: Institute of Hematology, Sacred Heart Catholic University of Rome, Rome, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Massini
authors.affiliation: Institute of Hematology, Sacred Heart Catholic University of Rome, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Maiolo
authors.affiliation: Institute of Hematology, Sacred Heart Catholic University of Rome, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Guidi
authors.affiliation: Institute of Hematology, Sacred Heart Catholic University of Rome, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cupelli
authors.affiliation: Institute of Pathological Anatomy, Sacred Heart Catholic University of Rome, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.affiliation: Institute of Pathological Anatomy, Sacred Heart Catholic University of Rome, Rome, Italy.
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Larocca
authors.affiliation: Institute of Hematology, Sacred Heart Catholic University of Rome, Rome, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Voso
authors.affiliation: Institute of Hematology, Sacred Heart Catholic University of Rome, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Leone
authors.affiliation: Institute of Hematology, Sacred Heart Catholic University of Rome, Rome, Italy. Electronic address: stefan.hohaus@rm.unicatt.it.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hohaus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases / Q000235:genetics*; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008745:Methylation; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods
chemical_list: C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases