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Lenalidomide + decitabine is a combination therapy used primarily in the treatment of myelodysplastic syndromes (MDS), particularly in patients with del(5q) and excess blasts. Lenalidomide is an immunomodulatory agent that acts by altering cytokine production, regulating T cell co-stimulation, enhancing NK cell-mediated cytotoxicity, and directly inhibiting the cullin ring E3 ubiquitin ligase complex via binding to cereblon. This leads to degradation of key transcription factors involved in malignant B-cell survival[3][6]. Decitabine is a pyrimidine nucleoside analogue that incorporates into DNA after phosphorylation and inhibits DNA methyltransferases, resulting in global hypomethylation and reactivation of tumor suppressor genes[2]. The combination leverages distinct mechanisms—epigenetic modulation by decitabine and immunomodulation plus direct anti-tumor effects by lenalidomide—to potentially improve outcomes for high-risk MDS patients[1][5].
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