DIS3 gene mutations (DIS3mts) occur in roughly 10% of multiple myeloma (MM) patients; furthermore, DIS3 expression could be affected by monosomy 13 or del(13q), which occur in approximately 40% of MM cases. Despite several reports on the prevalence of DIS3mts, their contribution to the pathobiology of MM remains largely unknown. We took advantage of the large public CoMMpass dataset to investigate the spectrum of DIS3mts in MM and its impact on the transcriptome and clinical outcome. We found that DIS3mts clinical relevance strictly depended on del(13q) co-occurrence. In particular, bi-allelic DIS3 lesions significantly affected PFS, independently from other predictors of poor clinical outcome, while mono-allelic events mostly impacted OS. As expected, DIS3mts affect MM transcriptome involving cellular processes and signaling pathways associated with RNA metabolism, and the deregulation of a large number of lncRNAs, among which we identified five distinct transcripts as independent predictors of poorer OS and nine of worse PFS, some of which (AC015982.2 and AL445228.3) predicting both. These findings strongly prompt further studies investigating the relevance of these lncRNAs in MM.
The biological role and therapeutic potential of long non-coding RNAs (lncRNAs) in chronic lymphocytic leukemia (CLL) are still open questions. Herein, we investigated the significance of the lncRNA NEAT1 in CLL. We examined NEAT1 expression in 310 newly diagnosed Binet A patients, in normal CD19+ B-cells, and other types of B-cell malignancies. Although global NEAT1 expression level was not statistically different in CLL cells compared to normal B cells, the median ratio of NEAT1_2 long isoform and global NEAT1 expression in CLL samples was significantly higher than in other groups. NEAT1_2 was more expressed in patients carrying mutated IGHV genes. Concerning cytogenetic aberrations, NEAT1_2 expression in CLL with trisomy 12 was lower with respect to patients without alterations. Although global NEAT1 expression appeared not to be associated with clinical outcome, patients with the lowest NEAT1_2 expression displayed the shortest time to first treatment; however, a multivariate regression analysis showed that the NEAT1_2 risk model was not independent from other known prognostic factors, particularly the IGHV mutational status. Overall, our data prompt future studies to investigate whether the increased amount of the long NEAT1_2 isoform detected in CLL cells may have a specific role in the pathology of the disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.