This study sought to identify novel targets for the treatment of patients with del(5q) MDS by performing an in vivo drug screen using an rps14-deficient zebrafish model.
In investigating the cause of GATA1 downregulation, our gene-expression study revealed the presence of the RPS14-deficient gene signature, which is associated with defective ribosomal protein function and linked to the erythroid lineage in 5q deletion myelodysplastic syndrome.
Our data link Rps14 haploinsufficiency in del(5q) MDS to activation of the innate immune system and induction of S100A8-S100A9 expression, leading to a p53-dependent erythroid differentiation defect.
Haploinsufficiency of the ribosomal protein gene RPS14 plays a critical role in the development of anemia in the 5q- syndrome, and haploinsufficiency of CUX1 is important in some patients with MDS and AML with complete or partial loss of chromosome 7.
While establishing a cell culture model for myelodysplastic syndrome with a deletion in 5q by performing RPS14 knockdown, we found surprising data that may be of importance for any CD34+ cell culture experiments.
Changes in miR-143, miR-145, miR-146a, miR-146b, miR-378, miR-584, SPARC and RPS14 were examined in del(5q) (n=10) and non-del(5q) (n=18) myelodysplastic syndrome patient samples.
This study was carried out to investigate RPS14 expression in MDS without 5q deletion and the role of lower expressed RPS14 plays in pathogenesis and the prognosis and lenalidomide-response predicting of non-5q-MDS.
Diminutive mosaic deletions involving RPS14 were identified in a 5-year-old patient with nonclassical DBA and in a 17-year-old patient with myelodysplastic syndrome.
Allelic deletion of the RPS14 gene is a key effector of the hypoplastic anemia in patients with myelodysplastic syndrome (MDS) and chromosome 5q deletion (del(5q)).
Accordingly, in addition to classical oncogenic abnormalities, such as p53 abnormalities, or NRAS mutation, various molecular abnormalities, such as TET2, RPS14, or c-CBL, have been identified and/or proposed as the novel candidates for molecular basis of the development and progression of MDS.
MDS patients with an intermediate-1 risk (INT-1) score according to the international prognostic scoring system and low RPS14 expression had a superior median overall survival of not reached versus 25 months compared to INT-1 patients with high RPS14 expression (p=0.0249).