title: 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.
authors.affiliation: Hematology Division, Sixth Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Wu
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Chunkang
authors.initials: C
authors.lastname: Chang
authors.forename: Qi
authors.initials: Q
authors.lastname: He
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000096:biosynthesis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism*; D003561:Cytarabine / Q000627:therapeutic use; D000077209:Decitabine; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006248:Harringtonines / Q000627:therapeutic use; D000077863:Homoharringtonine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D012269:Ribosomal Proteins / Q000096:biosynthesis*; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D006248:Harringtonines; D012269:Ribosomal Proteins; C032493:ribosomal protein L17; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D000077863:Homoharringtonine; D000077209:Decitabine; D001374:Azacitidine