Vorinostat synergizes with antioxidant therapy to target myeloproliferative neoplasms.

Abstract:

:BCR-ABL-negative myeloproliferative neoplasms (MPNs) are driven by JAK-STAT pathway activation, but epigenetic alterations also play an important pathophysiological role. These can be pharmacologically manipulated with histone deacetylase inhibitors (HDACIs), which have proven to be clinically effective in the treatment of MPNs but exhibit dose-limiting toxicity. The treatment of primary MPN cells with vorinostat modulates the expression of genes associated with apoptosis, cell cycle, inflammation, and signaling. The induction of this transcriptional program results in decreased cellular viability, paralleled by a decrease in levels of reactive oxygen species (ROS). In vitro manipulation of ROS levels revealed that the reduction of ROS levels promoted apoptosis. When vorinostat was combined with antioxidant agents, the apoptosis of MPN cells increased in a synergistic manner. The results described here suggest a novel and promising therapeutic strategy combining HDACIs with ROS-reducing agents to treat MPNs.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Cardoso BA,Ramos TL,Belo H,Vilas-Boas F,Real C,Almeida AM

doi

10.1016/j.exphem.2019.02.002

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

60-71.e11

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(19)30069-4

journal_volume

72

pub_type

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