TY - JOUR
T1 - Decitabine in myelodysplastic syndromes
AU - Jabbour, Elias
AU - Kantarjian, Hagop M.
AU - Garcia-Manero, Guillermo
AU - Issa, Jean Pierre J.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/11
Y1 - 2005/11
N2 - Decitabine (5-aza-2′-deoxycytidine), a cytosine analog, inhibits DNA methylation and has dual effects on neoplastic cells, including the reactivation of silenced genes and differentiation at low doses, and cytotoxicity at high doses. Decitabine has promising clinical efficacy in the treatment of myelodysplastic syndromes (a heterogeneous group of bone marrow malignancies), with evidence of target modulation (hypomethylation) and a favorable toxicity profile. Optimal dosing schedules of decitabine in myelodysplastic syndrome are those that maximize hypomethylation (low dose, high dose intensity, multiple cycles). However, the molecular mechanisms of in vivo response to decitabine are still unclear. Combination therapies that augment decitabine's epigenetic effect, or take advantage of gene activation, will likely improve clinical responses and may extend its use to the treatment of other malignancies.
AB - Decitabine (5-aza-2′-deoxycytidine), a cytosine analog, inhibits DNA methylation and has dual effects on neoplastic cells, including the reactivation of silenced genes and differentiation at low doses, and cytotoxicity at high doses. Decitabine has promising clinical efficacy in the treatment of myelodysplastic syndromes (a heterogeneous group of bone marrow malignancies), with evidence of target modulation (hypomethylation) and a favorable toxicity profile. Optimal dosing schedules of decitabine in myelodysplastic syndrome are those that maximize hypomethylation (low dose, high dose intensity, multiple cycles). However, the molecular mechanisms of in vivo response to decitabine are still unclear. Combination therapies that augment decitabine's epigenetic effect, or take advantage of gene activation, will likely improve clinical responses and may extend its use to the treatment of other malignancies.
KW - Decitabine
KW - Epigenetic therapy
KW - Methylation
KW - Myelodysplastic syndrome
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U2 - 10.1586/14750708.2.6.835
DO - 10.1586/14750708.2.6.835
M3 - Article
AN - SCOPUS:28344455628
SN - 1475-0708
VL - 2
SP - 835
EP - 842
JO - Therapy
JF - Therapy
IS - 6
ER -