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A combination therapy consisting of the selective inhibitor of nuclear export (SINE) selinexor and the hypomethylating agent azacitidine. Selinexor is a first-in-class, oral small molecule that covalently binds to and inhibits Exportin 1 (XPO1), a protein responsible for the nuclear-to-cytoplasmic export of tumor suppressor proteins and growth-regulatory factors. By blocking XPO1, selinexor promotes the nuclear accumulation and activation of tumor suppressors, leading to apoptosis in malignant cells. Azacitidine is a pyrimidine nucleoside analog that acts as a DNA methyltransferase inhibitor; it incorporates into DNA and RNA, causing DNA hypomethylation and direct cytotoxicity, which helps restore normal hematopoiesis. This combination is being investigated as a maintenance therapy for patients with TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) following allogeneic hematopoietic cell transplantation to reduce the high risk of relapse in this specific molecular subpopulation.
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