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Azacitidine is a cytidine nucleoside analogue1 that is incorporated into newly synthesized DNA as well as RNA.1 Preclinical studies suggest that the antileukemic effects of azacitidine include direct cytotoxicity due to inhibition of protein synthesis and DNA damage and re-expression of aberrantly silenced tumor suppressor genes due to DNA hypomethylation.1-3
Azacitidine Hypothesized Mechanism of Action
Azacitidine is an epigenetic modifying therapy hypothesized to re-activate aberrantly silenced tumor suppressor genes and induce malignant cell death in acute myeloid leukemia.
Patients with acute myeloid leukemia (AML) have a poor prognosis, intensified by age-related factors and adverse disease characteristics.4-7 Intensive chemotherapy induction is standard treatment for AML but depends on patient fitness.6-8 The majority of patients who are ineligible or unfit for intensive chemotherapy are elderly,4,6-8 and their prognosis remains dismal.5 There is an unmet need for additional treatment options for patients with AML who are ineligible or unwilling to receive intensive chemotherapy.5 Preclinical studies in leukemia cell lines have demonstrated that treatment with azacitidine resulted in DNA demethylation, which supports its clinical investigation in AML.9