Among these patients, 784 patients had at least two GEP performed during their disease course including 147 patients with a paired diagnosis and relapse sample. Keywords: gene expression; myeloma; risk factors EN gene expression myeloma risk factors 283 286 4 10/12/21 20211015 NES 211015 Clustering of gene expression profiling (GEP) signatures at diagnosis identified a number of distinct biological subgroups that correlate with clinical outcome in multiple myeloma (MM).1-4 Some of these clusters are defined by an aetiologic genetic event whereas others, such as the proliferation cluster (PR) and GEP70 risk, relate to acquired transcriptional patterns associated with adverse clinical behaviour irrespective of the underlying disease subgroup.1,2 Much has been written about the GEP70 risk classification but less has been presented about the PR cluster which is of particular importance as it was identified by the very first unsupervised clustering analysis2 and confirmed in other datasets.5 Key features of this group include the expression of typical proliferation genes and an adverse clinical outcome.6 The evolutionary behaviour of MM is now more clearly understood as is the natural history of MM which is associated with increasingly short periods of remission. High-risk transcriptional profiles in multiple myeloma are an acquired feature that can occur in any subtype and more frequently with each subsequent relapse. [Extracted from the article]