Changes in RPS14 expression levels during lenalidomide treatment in Low- and Intermediate-1-risk myelodysplastic syndromes with chromosome 5q deletion.

Abstract

BACKGROUND:

Haploinsufficiency of the ribosomal protein S14 RPS14 gene, located in the common deleted region of chromosome 5q, is a potential causal factor of 5q- syndrome. Lenalidomide elicits high response rates and morphological improvements in myelodysplastic syndrome (MDS) patients with chromosome 5q deletion [del(5q)].

METHODS:

To further evaluate the role of RPS14, its transcription was tested in bone marrow cells from 17 patients with International Prognostic Scoring System defined Low- or Intermediate-1-risk MDS with del(5q) as a single or additional cytogenetic abnormality receiving treatment with lenalidomide.

RESULTS:

After 12 wk of lenalidomide treatment, erythroid responses were observed in all cases with an increase in hemoglobin levels of 2.7 +/- 2.5 g/dL (up to a mean 11.8 +/- 1.9 g/dL; P = 0.001). Before treatment, RPS14 expression levels were under-expressed in 15 patients with respect to normal controls. After 12 wk of lenalidomide treatment, all patients had an erythroid response. There was a significant increase in median RPS14 expression from baseline 0.01 (IQR 0.05-0.31) to 12 wk 204.71-fold (2.86-446.32; P < 0.0001).

CONCLUSIONS:

These observations in the patient setting support the importance of RPS14 in the pathogenesis of MDS with del(5q).

• Authors: Esther N Oliva, Maria Cuzzola, Francesco Nobile, Francesca Ronco, Maria Grazia D'Errigo, Carmelo Laganà, Fortunato Morabito, Sara Galimberti, Agostino Cortelezzi, Maria A Aloe Spiriti, Giorgina Specchia, Antonella Poloni, Massimo Breccia, Riccardo Ghio, Carlo Finelli, Pasquale Iacopino, Giuliana Alimena, Roberto Latagliata
• Journal: European journal of haematology (Eur J Haematol) Vol. 85 Issue 3 Pg. 231-5 (Sep 2010) ISSN: 1600-0609 [Electronic] England
• PMID: 20491881 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• RPS14 protein, human
• Ribosomal Proteins
• Thalidomide
• Lenalidomide

Topics

• Aged
• Chromosome Deletion
• Chromosomes, Human, Pair 5 (genetics)
• Cytogenetic Analysis
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lenalidomide
• Male
• Myelodysplastic Syndromes (drug therapy, genetics)
• Ribosomal Proteins (genetics)
• Risk Factors
• Thalidomide (analogs & derivatives, therapeutic use)
• Transcription, Genetic (drug effects, genetics)