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This is a combination chemotherapy regimen consisting of three agents—bortezomib, homoharringtonine, and cytarabine—used primarily in the treatment of refractory or relapsed acute myeloid leukemia (AML). - **Bortezomib** is a small molecule proteasome inhibitor that disrupts protein degradation pathways, leading to apoptosis in cancer cells. - **Homoharringtonine** (HHT) is a plant alkaloid that inhibits protein synthesis by binding to the ribosomal A-site, resulting in cell cycle arrest and apoptosis. It also interferes with multiple signaling pathways including IL-6/JAK1/STAT3 and downregulates anti-apoptotic proteins such as Mcl-1[5]. - **Cytarabine** is an antimetabolite chemotherapeutic agent that inhibits DNA synthesis by acting as a cytosine nucleoside analog. The combination has demonstrated synergistic effects in preclinical studies, notably enhancing apoptosis through inhibition of Akt and NF-κB signaling pathways, activation of caspase 9/caspase 3, upregulation of Bax protein, downregulation of Bcl-2 family proteins, and modulation of p53 levels[3][5]. Clinical trials have shown promising efficacy for this regimen in patients with refractory or relapsed AML[1][4][6][8].
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