Differential expression of ribosomal proteins in myelodysplastic syndromes

Abstract

Aberrations of ribosomal biogenesis have been implicated in several congenital bone marrow failure syndromes, such as Diamond-Blackfan anaemia, Shwachman-Diamond syndrome and Dyskeratosis Congenita. Recent studies have identified haploinsufficiency of RPS14 in the acquired bone marrow disease isolated 5q minus syndrome, a subtype of myelodysplastic syndromes (MDS). However, the expression of various proteins comprising the ribosomal subunits and other proteins enzymatically involved in the synthesis of the ribosome has not been explored in non-5q minus MDS. Furthermore, differences in the effects of these expression alterations among myeloid, erythroid and megakaryocyte lineages have not been well elucidated. We examined the expression of several proteins related to ribosomal biogenesis in bone marrow biopsy specimens from patients with MDS (5q minus patients excluded) and controls with no known myeloid disease. Specifically, we found that there is overexpression of RPS24, DKC1 and SBDS in MDS. This overexpression is in contrast to the haploinsufficiency identified in the congenital bone marrow failure syndromes and in acquired 5q minus MDS. Potential mechanisms for these differences and aetiology for these findings in MDS are discussed.

Displacement of WDR5 from Chromatin by a WIN Site Inhibitor with Picomolar Affinity

“…Perhaps the most intriguing application of WIN site inhibitors, however, relates to their ability to inhibit RPG transcription. The concept of targeting ribosome biosynthesis has gained momentum in recent years as a viable strategy to treat cancer ( Pelletier et al, 2018 ), and may hold promise in other diseases of ribosome dysfunction, such as myelodysplastic syndrome ( Rinker et al, 2016 ). Most of the successes in this area have centered on the inhibition of ribosomal RNA transcription ( Bruno et al, 2017 ).…”

Contributions of transcriptional noise to leukaemia evolution: KAT2A as a case-study

“…Several RPs are mutated in cancer and/or differentially associate with survival. Heterozygous RP mutations are causal of a subset of myelodysplastic syndromes [ 134 , 135 ] and ribosomal defects are central to congenital anaemias with leukaemia predisposition [ 136 , 137 ]. RPL22 deletion is the most commonly deleted RP in cancer, and is specifically associated with T-cell leukaemia [ 138 ].…”