title: Aberrant DNA methylation profile of chronic and transformed classic Philadelphia-negative myeloproliferative neoplasms.
abstract: Most DNA methylation studies in classic Philadelphia-negative myeloproliferative neoplasms have been performed on a gene-by-gene basis. Therefore, a more comprehensive methylation profiling is needed to study the implications of this epigenetic marker in myeloproliferative neoplasms. Here, we have analyzed 71 chronic (24 polycythemia vera, 23 essential thrombocythemia and 24 primary myelofibrosis) and 13 transformed myeloproliferative neoplasms using genome-wide DNA methylation arrays. The three types of chronic Philadelphia-negative myeloproliferative neoplasms showed a similar aberrant DNA methylation pattern when compared to control samples. Differentially methylated regions were enriched in a gene network centered on the NF-κB pathway, indicating that they may be involved in the pathogenesis of these diseases. In the case of transformed myeloproliferative neoplasms, we detected an increased number of differentially methylated regions with respect to chronic myeloproliferative neoplasms. Interestingly, these genes were enriched in a list of differentially methylated regions in primary acute myeloid leukemia and in a gene network centered around the IFN pathway. Our results suggest that alterations in the DNA methylation landscape play an important role in the pathogenesis and leukemic transformation of myeloproliferative neoplasms. The therapeutic modulation of epigenetically-deregulated pathways may allow us to design targeted therapies for these patients.
authors.affiliation: Laboratory of Myeloproliferative Syndromes, Oncology Area, Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Pérez
authors.forename: Marien
authors.initials: M
authors.lastname: Pascual
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Martín-Subero
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bellosillo
authors.forename: Victor
authors.initials: V
authors.lastname: Segura
authors.forename: Eric
authors.initials: E
authors.lastname: Delabesse
authors.forename: Sara
authors.initials: S
authors.lastname: Álvarez
authors.forename: María José
authors.initials: MJ
authors.lastname: Larrayoz
authors.forename: José
authors.initials: J
authors.lastname: Rifón
authors.forename: Juan Cruz
authors.initials: JC
authors.lastname: Cigudosa
authors.forename: Carles
authors.initials: C
authors.lastname: Besses
authors.forename: María José
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
authors.forename: Xabier
authors.initials: X
authors.lastname: Agirre
mesh_terms: D002908:Chronic Disease; D019175:DNA Methylation / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000235:genetics; D011087:Polycythemia Vera / Q000175:diagnosis / Q000235:genetics*; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000235:genetics*