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This combination therapy, consisting of omacetaxine mepesuccinate, azacitidine, and granulocyte colony-stimulating factor (G-CSF), was investigated by the University of Florida in a Phase I/II clinical trial for the treatment of relapsed and/or refractory myelodysplastic syndromes (MDS). Omacetaxine mepesuccinate is a first-in-class protein synthesis inhibitor that binds to the A-site of the 80S ribosome, preventing the correct positioning of aminoacyl-tRNA and thus inhibiting the translation of short-lived oncoproteins such as BCR-ABL and MCL-1. Azacitidine is a hypomethylating agent that incorporates into DNA and RNA, where it covalently binds and inhibits DNA methyltransferases, leading to the reactivation of tumor suppressor genes and direct cytotoxicity. G-CSF is a hematopoietic growth factor that stimulates the production and differentiation of granulocytes; in this combination, it is used to manage neutropenia and potentially increase the sensitivity of leukemic blasts to the cytotoxic effects of the other agents.
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