Open AccessEpigenetic therapy in myeloproliferative neoplasms: evidence and perspectives
Author(s) -
Vannucchi Alessandro M.,
Guglielmelli Paola,
Rambaldi Alessandro,
Bogani Costanza,
Barbui Tiziano
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00827.x
Subject(s) - epigenetics , myelofibrosis , biology , epigenetic therapy , janus kinase 2 , cancer research , myeloproliferative disorders , microrna , polycythemia vera , carcinogenesis , dna methylation , cancer , medicine , bioinformatics , immunology , genetics , gene , gene expression , bone marrow
• The myeloproliferative neoplasms • The molecular pathogenesls of MPN • Epigenetic events In cancer • Epigenetic events In MPN • Drugs for epigenetic therapy • Epigenetic therapy In MPN • ConclusionsThe classic Philadelphia chromosome‐negative myeloproliferative neoplasms (MPNs), which include polycythaemia vera, essential thrombocythaemia and primary myelofibrosis, originate from a stem cell‐derived clonal myeloproliferation that manifests itself with variable haematopoietic cell lineage involvement; they are characterized by a high degree of similarities and the chance to transform each to the other and to evolve into acute leukaemia. Their molecular pathogenesis has been associated with recurrent acquired mutations in janus kinase 2 (JAK2) and myeloproliferative leukemia virus oncogene (MPL). These discoveries have simplified the diagnostic approach and provided a number of clues to understanding the phenotypic expression of MPNs; furthermore, they represented a framework for developing and/or testing in clinical trials small molecules acting as tyrosine kinase inhibitors. On the other hand, evidence of abnormal epigenetic gene regulation as a mechanism potentially contributing to the pathogenesis and the phenotypic diversity of MPNs is still scanty; however, study of epigenetics in MPNs represents an active field of research. The first clinical trials with epigenetic drugs have been completed recently, whereas others are still ongoing; results have been variable and at present do not allow any firm conclusion. Novel basic and translational information concerning epigenetic gene regulation in MPNs and the perspectives for therapy will be critically addressed in this review.