Development of gene expression signatures for lenalidomide treatement on megakaryocyte

To clarify the machinery how lenalidomide inhibit proplatelet formation of megakaryocytes, we performed transcriptome analysis of megakaryocytes derived from human hematopoietic stem/progenitor cells in the liquid culture system with or without lenalidomide. Differentially expressed genes were comprehensively evaluated by gene set enrichment analysis. Untreated megakaryocytes showed the estradiol-responded gene expression signatures, whereas the lenalidomide-treated megakaryocytes did not. Furthermore, we performed a rescue strategy with exogenous estradiol, confirming that lenalidomide-induced inhibition of proplatelet formation should be due to the deficiency of endogenous estradiol action in megakaryocytes. Lenalidomide treatment-induced difference in gene expression profile of human megakaryocytes were evaluated. Megakaryocytes were generated from hematopoietic stem/progenitor cells of 4 individual healthy volunteers in the presence or absence of 10 µM lenalidomide.