Difference in gene expression signatures for progenies of lenalidomide-treated megakaryocyte/erythrocyte progenitors

To clarigy the molecular mechanism underlying the IMiD-induced megakaryocytic lineage commitment in human megakaryocyte/erythrocyte progenitors, we performed transcriptome analysis of CD41-CD105+ and CD41+CD105- cells obtained from megakaryocyte/erythrocyte progenitors treated with lenalidomide for 72 hours. Differentially expressed genes were comprehensively evaluated by gene set enrichment analysis. CD105-CD41+ cells showed the enrichment in the expression of genes related to megakaryocytes and platelet, whereas genes related to erythroid lineage were negatively enriched. CD41+CD105- cells expressed higher levels of transcription factors required for megakaryocyte differentiation including FLI1, RUNX1, and MEIS1. Furthermore, we performed a knockdown strategy with small interfering RNA against MEIS1 mRNA, confirming that lenalidomide-induced megakaryocyte commitment should be due to the up-regulation of MEIS1 in megakaryocyte/erythrocyte progenitors. Difference in gene expression profile of CD105+ progenies and CD41+ progenies derived from lenalidomide-treated human megakaryocyte/erythrocyte progenitors were evaluated. Progenies were generated from megakayrocyte/erythrocyte progenitors of 4 individual healthy volunteers by 72-hour incubation with 10 µM lenalidomide.