Equitoxic doses of 5-azacytidine and 5-aza-2'deoxycytidine induce diverse immediate and overlapping heritable changes in the transcriptome

Xiangning Qiu, Christoffer Hother, Ulrik M Ralfkiær, Alexandra Søgaard, Qianjin Lu, Christopher Workman, Gangning Liang, Peter A Jones, Kirsten Grønbæk

    65 Citationer (Scopus)

    Abstract

    The hypomethylating agent 5-Azacytidine (5-Aza-CR) is the first drug to prolong overall survival in patients with myelodysplastic syndrome (MDS). Surprisingly, the deoxyribonucleoside analog 5-Aza-2'deoxycytidine (5-Aza-CdR) did not have a similar effect on survival in a large clinical trial. Both drugs are thought to exert their effects after incorporation into DNA by covalent binding of DNA methyltransferase (DNMT). While 5-Aza-CdR is incorporated into only DNA, 5-Aza-CR is also incorporated into RNA. Here, we have analyzed whether this difference in nucleic acid incorporation may influence the capacities of these drugs to regulate the expression of mRNA and microRNAs (miRNA), which may potentially affect the activities of the drugs in patients.
    OriginalsprogEngelsk
    TidsskriftP L o S One
    Vol/bind5
    Udgave nummer9
    Sider (fra-til)e12994
    ISSN1932-6203
    DOI
    StatusUdgivet - 1 jan. 2010

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