MMSET: Role and Therapeutic Opportunities in Multiple Myeloma

Recurrent chromosomal translocations are central to the pathogenesis, diagnosis, and prognosis of hematologic malignancies. The translocation t(4; 14)(p16; q32) is one of the most common translocations in multiple myeloma (MM) and is associated with very poor prognosis. The t(4; 14) translocation leads to the simultaneous overexpression of two genes, FGFR3 (fibroblast growth factor receptor 3) and MMSET (multiple myeloma SET domain), both of which have potential oncogenic activity. However, approximately 30% of t(4; 14) MM patients do not express FGFR3 and have poor prognosis irrespective of FGFR3 expression, whereas MMSET overexpression is universal in t(4; 14) cases. In this review, we provide an overview of recent findings regarding the oncogenic roles of MMSET in MM and its functions on histone methylation. We also highlight some of MMSET partners and its downstream signalling pathways and discuss the potential therapeutics targeting MMSET.