Our analysis, involving a correlation between JAG1 or JAG2 gene expression and clinical data from 767 MM patients (CoMMpass database), unveiled a positive association between JAG2 expression levels and an increased risk of death and disease progression, independently from other known genetic prognostic factors such as older age, ISS stage III, and distinct molecular variables such as del(1p)/CDKN2C, del(13q)/RB1, 1q gain/amplification alone or in combination with TP53 alterations, t(4;14) translocation, MYC translocation, and the presence of DIS3 mutations. Here, RB1 is linked to Miyoshi myopathy.