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Current Cancer Drug Targets


ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Hypomethylating Agents in the Treatment of Myelodysplastic Syndromes and Myeloid Leukemia

Author(s): Anna Szmigielska-Kaplon and Tadeusz Robak

Volume 11, Issue 7, 2011

Page: [837 - 848] Pages: 12

DOI: 10.2174/156800911796798940

Price: $65


Epigenetic changes play an important role in cancer pathogenesis. Hypermethylation of DNA generally results in decreased expression of tumor suppressor genes and defective cell cycle control. This is a hallmark of myelodysplastic syndromes (MDS) and acute myeloid leukemia. Fortunately, epigenetic changes are potentially reversible and thus remain an attractive target for anticancer therapy. Inhibitors of DNA methyltransferase cause demethylation of DNA and exert their activity in myelodysplastic syndromes and acute myeloid leukemia with good safety profile. Decitabine and azacytidine are approved for treatment of patients with high-risk MDS. Demethylating agents seem to be the best choice for elderly patients with myelodysplastic syndromes and acute myeloid leukemia, even in case of high risk cytogenetic changes in the karyotype. The mechanisms of action, pharmacokinetics and antileukemic activity of azacytidine and decitabine are the subjects of this review.

Keywords: Myelodysplastic syndromes, acute myeloid leukemia, hypomethylating agents, azacytidine, decitabine, elderly, Cancer and Leukemia Group B, graft versus host reaction, graft versus leukemia effect, myelodysplastic syndrome

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