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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.

journal_name

Haematologica

journal_title

Haematologica

authors

Pérez C,Pascual M,Martín-Subero JI,Bellosillo B,Segura V,Delabesse E,Álvarez S,Larrayoz MJ,Rifón J,Cigudosa JC,Besses C,Calasanz MJ,Cross NC,Prósper F,Agirre X

doi

10.3324/haematol.2013.084160

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

1414-20

issue

9

eissn

0390-6078

issn

1592-8721

pii

haematol.2013.084160

journal_volume

98

pub_type

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