Targeting the IRF4 Transcriptional Network to Subvert Multiple Myeloma

Multiple Myeloma (MM) is an incurable hematologic malignancy characterised by the abnormal proliferation of plasma cells.

Interferon Regulatory Factor 4 (IRF4), a transcription factor essential for immune system regulation and plasma cell differentiation, has emerged as the master regulator of an aberrant gene expression programme in MM. Overexpression of IRF4 is found in MM patients’ derived cells, where it is key to their survival.

Accumulating evidence suggests that IRF4 and MYC regulate each other in MM cell lines, creating a positive regulatory loop resulting in the proliferation of MM cells. Despite its major role, key elements of the mechanism of action of IRF4 in the context of MM have not been clearly elucidated.

The aim of our work is to lay the groundwork towards targeting IRF4 to subvert MM. Our results point at yet uncovered regulatory interactions within the IRF4 network and provide key insights into the DNA binding specificity and affinity in the context of MM.