Changes in RPS14 expression levels during lenalidomide treatment in Low- and Intermediate-1-risk myelodysplastic syndromes with chromosome 5q deletion.
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).
Oliva
Esther N
EN
Hematology Unit, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy. estheroliva@hotmail.com
Cuzzola
Maria
M
Nobile
Francesco
F
Ronco
Francesca
F
D'Errigo
Maria Grazia
MG
Laganà
Carmelo
C
Morabito
Fortunato
F
Galimberti
Sara
S
Cortelezzi
Agostino
A
Aloe Spiriti
Maria A
MA
Specchia
Giorgina
G
Poloni
Antonella
A
Breccia
Massimo
M
Ghio
Riccardo
R
Finelli
Carlo
C
Iacopino
Pasquale
P
Alimena
Giuliana
G
Latagliata
Roberto
R
D000368:Aged; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D020732:Cytogenetic Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics*; D012307:Risk Factors; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
C526722:RPS14 protein, human; D012269:Ribosomal Proteins; D013792:Thalidomide; D000077269:Lenalidomide