ABSTRACT
Objective:To explore the expression of fructose bisphosphate aldolase A (ALDOA) in the bone marrow of patients with acute myeloid leukemia (AML) and the correlation with clinical features and prognosis.Methods:The bone marrow samples of 90 newly diagnosed AML (non-acute promyelocytic leukemia) patients and 18 allogeneic hematopoietic stem cell transplantation donors who were treated from January 2013 to December 2015 in the First Affiliated Hospital of Zhengzhou University and the Children's Hospital Affiliated to Zhengzhou University were collected. The relative expression level of ALDOA mRNA in bone marrow samples was detected by using real-time quantitative polymerase chain reaction (qRT-PCR). Clinical data of these patients were retrospectively analyzed, and the patients were divided into continuous complete remission (CR) group and refractory recurrent (RR) group according to the clinical response and follow-up results. The differences of the relative expression level of ALDOA mRNA between AML group and the normal control group, CR group and RR group were analyzed. Univariate and multivariate Cox regression risk model were used for analysis of factors influencing prognosis of AML patients.Results:The relative expression level of ALDOA mRNA in AML group was higher than that in normal control group [(5.71±0.44) vs. (1.10±0.08), t = 4.74, P<0.001]. The relative expression level of ALDOA mRNA in the RR group was higher than that in the CR group [(6.69±0.67) vs. (4.30±0.36) , t = 2.79, P < 0.001]. In addition, there were statistically significant differences in the proportion of patients with ALDOA mRNA high expression and those with ALDOA mRNA low expression stratified by the number of white blood cell, the proportion of bone marrow blasts and whether complete remission could be achieved or not after 1 course of induction therapy (all P < 0.05). Overall survival in patients with ALDOA high expression was worse than that in patients with ALDOA low expression ( χ2 = 5.59, P = 0.018). Multivariate analysis showed that white blood cell count, prognosis stratification, whether complete remission could be achieved or not after 1 course of induction therapy and ALDOA expression were the independent prognostic factors for the death of AML patients (all P < 0.05). Conclusions:ALDOA may play an important role in the development and progression of AML, and the expression level of ALDOA in the bone marrow can be used as an index for the prognosis assessment of AML patients and may be a potential therapeutic target for AML.
ABSTRACT
Objective To preliminarily explore the effects of gene knock-out and overexpression of aldolase A on tumor cell proliferation, and then confirm the relationship between aldolase A and tumor growth during the process of anaerobic metabolism. Methods Through vector plasmid building and lentiviral infection, the cell lines stably overexpressing aldolase A and its gene knock- out cell lines were constructed respectively. The restructured cell lines were validated on gene and protein levels. Then, the changes of cell proliferation ratio were observed. Results Real time PCR results showed that aldolase A gene expression of the overexpressing cell line was about 3 times that of the normal cells. Among the five interfering targets of aldolase A designed according to aldolase A RNA sequences, aldolase A4 had more obvious interference effect on the target gene expression, the aldolase A mRNA level of which was about 1/50 of the normal cells. Compared with normal control group, the proliferation rate of aldolase A gene overexpression significantly increased by 40% in 48 h(P<0.05), while the proliferation rate of aldolase A gene knock out cells significantly de? creased about 86% in 24 h(P<0.05). Conclusion Aldolase A expressions have obvious effects on hepatocellular carcinoma cells.
ABSTRACT
Objective To preliminarily explore the effects of gene knock-out and overexpression of aldolase A on tumor cell proliferation,and then confirm the relationship between aldolase A and tumor growth during the process of anaerobic metabolism. Methods Through vector plasmid building and lentiviral infection,the cell lines stably overexpressing aldolase A and its gene knock-out cell lines were constructed respectively. The restructured cell lines were validated on gene and protein levels. Then ,the changes of cell proliferation ratio were observed. Results Real time PCR results showed that aldolase A gene expression of the overex?pressing cell line was about 3 times that of the normal cells. Among the five interfering targets of aldolase A designed according to aldol?ase A RNA sequences,aldolase A4 had more obvious interference effect on the target gene expression,the aldolase A mRNA level of which was about 1/50 of the normal cells. Compared with normal control group,the proliferation rate of aldolase A gene overexpression significantly increased by 40% in 48 h(P<0.05),while the proliferation rate of aldolase A gene knock out cells significantly de?creased about 86%in 24 h(P<0.05). Conclusion Aldolase A expressions have obvious effects on hepatocellular carcinoma cells.