Cargando…

Epigenetic therapy in myeloproliferative neoplasms: evidence and perspectives

The 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 invol...

Descripción completa

Detalles Bibliográficos
Autores principales: Vannucchi, Alessandro M, Guglielmelli, Paola, Rambaldi, Alessandro, Bogani, Costanza, Barbui, Tiziano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828857/
https://www.ncbi.nlm.nih.gov/pubmed/19522842
http://dx.doi.org/10.1111/j.1582-4934.2009.00827.x
_version_ 1782291295594610688
author Vannucchi, Alessandro M
Guglielmelli, Paola
Rambaldi, Alessandro
Bogani, Costanza
Barbui, Tiziano
author_facet Vannucchi, Alessandro M
Guglielmelli, Paola
Rambaldi, Alessandro
Bogani, Costanza
Barbui, Tiziano
author_sort Vannucchi, Alessandro M
collection PubMed
description The 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.
format Online
Article
Text
id pubmed-3828857
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher Blackwell Publishing Ltd
record_format MEDLINE/PubMed
spelling pubmed-38288572015-04-27 Epigenetic therapy in myeloproliferative neoplasms: evidence and perspectives Vannucchi, Alessandro M Guglielmelli, Paola Rambaldi, Alessandro Bogani, Costanza Barbui, Tiziano J Cell Mol Med Reviews The 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. Blackwell Publishing Ltd 2009-08 2009-06-11 /pmc/articles/PMC3828857/ /pubmed/19522842 http://dx.doi.org/10.1111/j.1582-4934.2009.00827.x Text en © 2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
spellingShingle Reviews
Vannucchi, Alessandro M
Guglielmelli, Paola
Rambaldi, Alessandro
Bogani, Costanza
Barbui, Tiziano
Epigenetic therapy in myeloproliferative neoplasms: evidence and perspectives
title Epigenetic therapy in myeloproliferative neoplasms: evidence and perspectives
title_full Epigenetic therapy in myeloproliferative neoplasms: evidence and perspectives
title_fullStr Epigenetic therapy in myeloproliferative neoplasms: evidence and perspectives
title_full_unstemmed Epigenetic therapy in myeloproliferative neoplasms: evidence and perspectives
title_short Epigenetic therapy in myeloproliferative neoplasms: evidence and perspectives
title_sort epigenetic therapy in myeloproliferative neoplasms: evidence and perspectives
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828857/
https://www.ncbi.nlm.nih.gov/pubmed/19522842
http://dx.doi.org/10.1111/j.1582-4934.2009.00827.x
work_keys_str_mv AT vannucchialessandrom epigenetictherapyinmyeloproliferativeneoplasmsevidenceandperspectives
AT guglielmellipaola epigenetictherapyinmyeloproliferativeneoplasmsevidenceandperspectives
AT rambaldialessandro epigenetictherapyinmyeloproliferativeneoplasmsevidenceandperspectives
AT boganicostanza epigenetictherapyinmyeloproliferativeneoplasmsevidenceandperspectives
AT barbuitiziano epigenetictherapyinmyeloproliferativeneoplasmsevidenceandperspectives