GSE113031
The IMiDs, through loss of Ikaros and Aiolos, primes myeloma cells for daratumumab mediated killing by upregulation of CD38
Recent studies have demonstrated that the immunomodulatory drugs (IMiDs) lead to the degradation of the transcription factors Ikaros and Aiolos. However, why their loss subsequently leads to multiple myeloma (MM) cell death remains unclear. Using CRISPR-Cas9 genome editing, we have deleted IKZF1 and IKZF3 in human MM cell lines to gain further insight into their downstream gene regulatory networks. Our findings strongly support the central role of Ikaros and Aiolos in the action of the IMiDs. Inactivation of either factor alone recapitulates the cell intrinsic action of the IMiDs, resulting in cell cycle arrest and induction of apoptosis. Furthermore, evaluation of the transcriptional changes resulting from their loss demonstrates striking overlap with lenalidomide treatment. Overall design: RNA sequencing data of human multiple myeloma cell lines 72hrs post CRISPR-Cas9 deletion of IKZF1 or IKZF3, or treatment with Lenalidomide 10µM.