Background: The myelodysplastic syndromes (MDS) are a group of stem cell disorders characterized by dysplasia of one or more hematopoietic cell lineages and a risk of progression to acute myeloid leukemia. The cytidine analog azacitidine (Vidaza), a hypomethylating agent, improves survival in patients with MDS, but its mechanism of action is not well understood.
Materials And Methods: The effects of azacitidine on the MDS-derived cell line SKM-1 were investigated by DNA methylation assay, cell proliferation assay, and a subcutaneous xenograft mouse model.
Results: Azacitidine and decitabine induced hypomethylation of the tumor suppressor gene cyclin-dependent kinase 4 inhibitor B (CDKN2B) in SKM-1 cells, whereas the deoxycytidine analog cytarabine did not. Azacitidine and decitabine also inhibited SKM-1 cell growth in vitro. In the mouse xenograft model, azacitidine significantly suppressed tumor growth.
Conclusion: Inhibition of DNA methyltransferase by azacitidine contributes to its antiproliferative and antitumor effects against SKM-1 cells and may explain its clinical efficacy in MDS.
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