MYC needs MNT to drive B cells over the edge

Abstract

MNT is a member of the MYC transcription factor network of proteins1 that must heterodimerize with MYC-associated factor X, or MAX for short, to bind certain DNA recognition motifs in gene promoters that regulate gene expression. Because many target genes that are activated by MYC:MAX dimers are repressed by MNT:MAX dimers, MNT is considered a transcriptional antagonist of MYC.2 However, the interaction of MNT and MYC goes further, beyond transcriptional antagonism, and governs a multitude of developmental pathways and cell fate decisions that include MNT's ability to fortify or weaken MYC's oncogenic potential depending on cell type and biological context.2 Previous work by Cory's group pointed to a synergistic interaction of MYC and MNT in neoplastic B-cell development,3 but the underlying mechanism remained unclear. In this issue of Blood, Nguyen et al4 have now addressed this knowledge gap with a follow-up study that identified MNT as a promising molecular target for the treatment and prevention of MYC-dependent B-cell neoplasms such as non-Hodgkin lymphoma and multiple myeloma. This is significant because at this juncture aberrant MYC expression stubbornly resists any attempt at therapeutic targeting.