Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterised by the clonal proliferation of the haematopoietic precursors together with the progressive development of bone marrow fibrosis. This stromal alteration is an important clinical issue and specific prognostic markers are not currently available. In bone marrow biopsies from 58 PMF patients, we explored the methylation pattern of genes encoding cytokines involved in the stromal reaction, namely platelet-derived growth factor-beta (PDGFB), transforming growth factor-beta (TGFB) and basic fibroblast growth factor (FGF2). We also evaluated the methylation profile of the Long Interspersed Nucleotide Element 1 (LINE-1). PDGFB, FGF2 and LINE-1, but not TGFB, were significantly differently methylated in PMF compared to controls. Significantly, PDGFB hypomethylation (<16%) was correlated with a favourable PMF prognosis (grade of marrow fibrosis, p=0.03; International Prognostic Scoring Systems p=0.01 and Dynamic International Prognostic Scoring Systems, p=0.02). Although the basis of the association of PDGFB hypomethylation with favourable prognosis remains to be clarified, we speculate that hypomethylation in PMF could represent the effect of acquired somatic mutations in genes involved in epigenetic regulation of the genome.

PDGFB hypomethylation is a favourable prognostic biomarker in primary myelofibrosis / C. Augello, U. Gianelli, R. Falcone, S. Tabano, F. Savi, E. Bonaparte, M. Ciboddo, L. Paganini, A. Parafioriti, D. Ricca, S. Lonati, D. Cattaneo, N. Fracchiolla, A. Iurlo, A. Cortelezzi, S. Bosari, M. Miozzo, S. Sirchia. - In: LEUKEMIA RESEARCH. - ISSN 0145-2126. - 39:2(2015 Feb), pp. 236-241.

PDGFB hypomethylation is a favourable prognostic biomarker in primary myelofibrosis

C. Augello;U. Gianelli;R. Falcone;S. Tabano;E. Bonaparte;L. Paganini;D. Cattaneo;N. Fracchiolla;A. Cortelezzi;S. Bosari;M. Miozzo;S. Sirchia
2015-02

Abstract

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterised by the clonal proliferation of the haematopoietic precursors together with the progressive development of bone marrow fibrosis. This stromal alteration is an important clinical issue and specific prognostic markers are not currently available. In bone marrow biopsies from 58 PMF patients, we explored the methylation pattern of genes encoding cytokines involved in the stromal reaction, namely platelet-derived growth factor-beta (PDGFB), transforming growth factor-beta (TGFB) and basic fibroblast growth factor (FGF2). We also evaluated the methylation profile of the Long Interspersed Nucleotide Element 1 (LINE-1). PDGFB, FGF2 and LINE-1, but not TGFB, were significantly differently methylated in PMF compared to controls. Significantly, PDGFB hypomethylation (<16%) was correlated with a favourable PMF prognosis (grade of marrow fibrosis, p=0.03; International Prognostic Scoring Systems p=0.01 and Dynamic International Prognostic Scoring Systems, p=0.02). Although the basis of the association of PDGFB hypomethylation with favourable prognosis remains to be clarified, we speculate that hypomethylation in PMF could represent the effect of acquired somatic mutations in genes involved in epigenetic regulation of the genome.
DNA methylation; FGF2; LINE-1; PDGFB; Primary myelofibrosis
Settore MED/03 - Genetica Medica
Settore MED/08 - Anatomia Patologica
Settore MED/15 - Malattie del Sangue
LEUKEMIA RESEARCH
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/252533
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