New insights into 5q-syndrome as a ribosomopathy

Myelodysplastic Syndromes (MDS) are a heterogeneous group of acquired clonal bone marrow disorders, characterised by ineffective hematopoiesis. The mechanisms underlying many of these blood disorders have remained elusive due to the difficulty in pinpointing specific gene mutations or haploinsufficencies, which can occur within large deleted regions. However, there is an increasing interest in the classification of some of these diseases as ribosomopathies. Indeed, studies have implicated Ribosomal Protein (RP) S14 as a strong candidate for haploinsufficiency in 5q-syndrome, a particular form of MDS. Recently, two novel mouse models have provided evidence for the involvement of both RPS14 and the p53 pathway, and specific miRNAs in 5q-syndrome. In this review we will discuss: 5q-syndrome mouse models, the possible mechanisms underlying this blood disorder with respect to the candidate genes and comparisons with other ribosomopathies and the involvement of the p53 pathway in these diseases.