Hydralazine and magnesium valproate as epigenetic treatment for myelodysplastic syndrome. Preliminary results of a phase-II trial

@article{Candelaria2010HydralazineAM,
  title={Hydralazine and magnesium valproate as epigenetic treatment for myelodysplastic syndrome. Preliminary results of a phase-II trial},
  author={Myrna Candelaria and Aquileo Herrera and Juan Labardini and Aurora Gonz{\'a}lez-Fierro and C Trejo-Becerril and Luc{\'i}a Taja-Chayeb and Enrique P{\'e}rez-C{\'a}rdenas and Erick de la Cruz-Hern{\'a}ndez and Daymi Arias-Bofill and Silvia Vidal and Eduardo E Cervera and Alfonso Due{\~n}as-Gonz{\'a}lez},
  journal={Annals of Hematology},
  year={2010},
  volume={90},
  pages={379-387}
}
Decitabine and azacitidine, two DNA methyltransferase (DNMT) inhibitors, are the current standard of treatment for myelodysplastic syndrome (MDS). Histone deacetylase (HDAC) inhibitors are also being tested against MDS. Both drug classes synergize in their gene reactivating and anticancer activities. The combination of hydralazine and valproate (Transkrip®), a DNMT and HDAC inhibitor, respectively), has been developed as epigenetic therapy under the drug repositioning concept. To evaluate the… 
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TLDR
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Antimetastatic effect of epigenetic drugs, hydralazine and valproic acid, in Ras-transformed NIH 3T3 cells
TLDR
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Epigenetic regulation in myelodysplastic syndromes: implications for therapy
TLDR
How non-intensive epigenetic therapy can ‘re-programme’ gene expression patterns of abnormal hematopoiesis in MDS is discussed, and combination therapies represent potentially effective options for intermediate-2 and high-risk MDS.
Valproic acid triggers erythro/megakaryocyte lineage decision through induction of GFI1B and MLLT3 expression.
TLDR
The data suggest that VPA sustains the expression of stemness-related markers in hematopoietic stem/progenitor cells and is able to interfere with hematopolietic lineage commitment by enhancing erythrocyte and megakaryocyte differentiation and by inhibiting the granulocyte and mono-macrophage maturation.
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