Over-expression of RPL23 in myelodysplastic syndromes is associated with apoptosis resistance of CD34+ cells and predicts poor prognosis and distinct response to CHG chemotherapy or decitabine

Abstract

Ribosomal protein (RP) L23 has been suggested to be a negative regulator of cell apoptosis. In the present study, we analyzed RPL23 expression in 169 patients with myelodysplastic syndrome (MDS) by using real-time PCR. The apoptosis of CD34(+) marrow cells was examined by flow cytometry, and the correlation between RPL23 expression levels and apoptosis in CD34(+) cells was assessed. We then analyzed the clinical significance of RPL23 expression for predicting disease progression and patient survival as well as therapeutic response in patients administered with a cytarabine, homoharringtonine, and G-CSF (CHG) regimen or decitabine therapy. Increased RPL23 expression was found in patients with higher-risk MDS than in patients with lower-risk disease (p = 0.004). RPL23 expression levels were found being inversely correlated with decreased apoptotic ratio of CD34(+) cells in higher-risk patients (r = -0.672, p < 0.001). Compared to patients with normal RPL23 expression levels, those with increased RPL23 expression presented higher rates of transformation to acute myeloid leukemia (p = 0.005) and reduced 2-year survival rates (p = 0.012). Multivariate regression analysis showed that RPL23 expression level was an independent predictor of prognosis, regardless of patient age, IPSS score, or hemoglobin level. Moreover, patients with RPL23 over-expression appeared to have lower response rates to CHG chemotherapy (p = 0.027) but similar response rates to decitabine treatment. In conclusion, the over-expression of RPL23 might confer apoptosis resistance in CD34(+) cells, which may lead to disease progression and adverse prognosis in MDS. Increased RPL23 expression was an inverse indicator for CHG regimen, but not for decitabine treatment.