RNA-seq of human multiple myeloma cell lines and cell lines with long-term exposure to lenalidomide

Multiple myeloma (MM) is a hematopoietic malignancy whose prognosis has been improved by immunomodulatory drugs (IMiDs); however, long-term exposure of these drugs caused drug resistance in MM patients. Here we applied RNA sequencing to analyze the novel mechanisms of the acquiring lenalidomide resistance in MM cell lines. Firstly, lenalidomide resistant cell lines were established by long-term exposure of lenalidomide nearly 1 year. Comparative analysis between resistant and sensitive cell lines revealed that the resistant cells secreted a greater number of exosomes and enhanced cell adhesion ability. By whole transcriptome analysis, snare interaction pathway, which was associated with exosome secretion, was enriched in lenalidomide resistant cell lines. Finally, we identified SORT1 and LAMP2, which increased exosome secretion and cell adhesion ability in lenalidomide resistant cells. Notably, silencing of SORT1 or LAMP2 ameliorated the lenalidomide sensitivity in the resistant cells. In conclusion, our results showed that exosome secretion via SORT1 or LAMP2 could induce cell adhesion, leading to the acquisition of lenalidomide resistance in MM. Lenalidomide resistant cell lines were established by long-term exposure of lenalidomide nearly 1 year. Lenalidomide resistant cell lines had an ability to attach their culture dishes, and their morphology were changed round to spindle shape. Total RNA was extracted from parental cells (KMS21, KMS27, KMS34) and lenalidomide resistant cell lines (KMS21R, KMS27R, KMS34R). RNA-seq was performed to characterize these cells in detail.