Phoebe K Mondala, Ashni A Vora, Tianyuan Zhou, Elisa Lazzari, Luisa Ladel, Xiaolin Luo, Youngsoo Kim, Caitlin Costello, A Robert MacLeod, Catriona H M Jamieson, Leslie A Crews
In multiple myeloma, inflammatory and anti-viral pathways promote disease progression and cancer stem cell generation. Using diverse pre-clinical models, we investigated the role of interferon regulatory factor 4 (IRF4) in myeloma progenitor regeneration. In a patient-derived xenograft model that recapitulates IRF4 pathway activation in human myeloma, we test the effects of IRF4 antisense oligonucleotides (ASOs) and identify a lead agent for clinical development (ION251). IRF4 overexpression expands myeloma progenitors, while IRF4 ASOs impair myeloma cell survival and reduce IRF4 and c-MYC expression...
January 14, 2021: Cell Stem Cell