Deactylase inhibition in myeloproliferative neoplasms.
Myeloproliferative neoplasms (MPN) are clonal haemopoietic progenitor cell disorders characterized by the proliferation of one or more of the haemopoietic lineages (myeloid, erythroid and/or megakaryocytic). The MPNs include eight haematological disorders: chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), systemic mastocytosis (SM), chronic eosinophilic leukemia, not otherwise specified (CEL, NOS), chronic neutrophilic leukemia (CNL), and unclassifiable MPN (MPN, U). Therapeutic interventions for MPNs include the use of tyrosine kinase inhibitors (TKIs) for BCR-ABL1(+) CML and JAK2 inhibitors for PV, ET and PMF. Histone deacetylase inhibitors (HDACi) are a novel class of drugs capable of altering the acetylation status of both histone and non-histone proteins, thereby affecting a repertoire of cellular functions in neoplastic cells including proliferation, differentiation, immune responses, angiogenesis and survival. Preliminary studies indicate that HDACi when used in combination with tyrosine kinase or JAK2 inhibitors may overcome resistance to the latter agents and enhance the pro-apoptotic effects on MPN cells. This review provides a review of pre-clinical and clinical studies that have explored the use of HDACi as potential therapeutics for MPNs.
Myeloma Research Group, Australian Centre for Blood Diseases, Alfred Hospital/Monash University, Commercial Road, Melbourne, Victoria, 3004, Australia.
Sridurga
S
Mithraprabhu
George
G
Grigoriadis
Tiffany
T
Khong
Andrew
A
Spencer
D000818:Animals; D044127:Epigenesis, Genetic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology*; D011379:Prognosis
D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases