Quantification of DAPK1 Promoter Methylation in Bone Marrow and Peripheral Blood as a Follicular Lymphoma Biomarker

Francesco D'Alo', Maurizio Martini, Luigi Maria Larocca, Stefan Hohaus, Manuela Giachelia, Valentina Bozzoli, Maria Chiara Tisi, Giuseppina Massini, Elena Maiolo, Francesco Guidi, Elisa Cupelli, Maria Teresa Voso, Giuseppe Leone

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12 Citazioni (Scopus)

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
Lingua originaleEnglish
pagine (da-a)467-476
Numero di pagine10
RivistaTHE JOURNAL OF MOLECULAR DIAGNOSTICS
Volume2014
DOI
Stato di pubblicazionePubblicato - 2014

Keywords

  • BIOMARKER
  • LYMPHOMA

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