Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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. 2258 Jul 51

Ribosomal protein (RP) L23 is a negative regulator of cellular apoptosis, and RPL23 overexpression is associated with abnormal apoptotic resistance in CD34+ cells derived from patients with higher-risk myelodysplastic syndrome (MDS). However, the mechanism underlying RPL23-induced apoptotic resistance in higher-risk MDS patients is poorly understood. In this study, we showed that reduced RPL23 expression led to suppressed cellular viability, increased apoptosis and G1-S cell cycle arrest. Gene microarray analysis comparing RPL23-knockdown and control cells identified an array of differentially expressed genes, of which, Miz-1, was upregulated with transactivation of the cell cycle inhibitors p15Ink4b and p21Cip1, and Miz-1's functional repressor, c-Myc, was downregulated. Cells derived from higher-risk MDS patients demonstrated consistently increased expression of RPL23 and c-Myc and decreased Miz-1 expression compared with cells from lower-risk patients. In conclusion, Miz-1-dependent induction of p15Ink4b and p21Cip1 was depressed with decreased Miz-1 and increased c-Myc expression under conditions of elevated RPL23 expression, leading to apoptotic resistance in higher-risk MDS patients. Because RPL23 is encoded by a target gene of c-Myc, the RPL23/Miz-1/c-Myc regulatory circuit provides a feedback loop that links efficient RPL23 expression with c-Myc's function to suppress Miz-1-induced Cdk inhibitors and thereby leads to apoptotic resistance in higher-risk MDS patients.
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PMID:Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome. 2853 3