Methionine synthase A2756G polymorphism influences pediatric acute lymphoblastic leukemia risk: a meta-analysis.

Plenty of studies have investigated the effect of methionine synthase (MTR) A2756G polymorphism on risk of developing pediatric acute lymphoblastic leukemia (ALL), but the available results were inconsistent. Therefore, a meta-analysis was conducted to derive a more precise estimation of the association between MTR A2756G polymorphism and genetic susceptibility to pediatric ALL. The PubMed, Embase, Google Scholar, Web of Science, ScienceDirect, Wanfang Databases and China National Knowledge Infrastructure were systematically searched to identify all the previous published studies exploring the relationship between MTR A2756G polymorphism and pediatric ALL risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the strength of association. Sensitivity analysis and publication bias were also systematically assessed. This meta-analysis finally included ten available studies with 3224 ALL cases and 4077 matched controls. The results showed that there was significant association between MTR A2756G polymorphism and risk of pediatric ALL in overall population (AG vs. AA: OR = 1.13, 95%CI = 1.02-1.26, P = 0.02; AG+GG vs. AA: OR = 1.13, 95%CI = 1.02-1.25, P = 0.01; G allele vs. A allele: OR = 1.10, 95%CI = 1.01-1.20, P = 0.03). In the stratification analyses by ethnicity, quality score and control source, significant association was found in Caucasians, population-based designed studies and studies assigned as high quality. In conclusion, this meta-analysis suggests that MTR A2756G polymorphism may influence the development risk of pediatric ALL in Caucasians. Future large scale and well-designed studies are required to validate our findings.

[Clinical Curative Efficacy of Lenalidomide Combined with Chemotherapy for Acute Leukemia and Its Impact on VEGF].

OBJECTIVE: To investigate the clinical efficacy of regimen consisting of lenalidomide combined with chemotherapy for acute leukemia and its impact on vascular endothilial growth factor (vEGF) and basic fibroblast growth factor (bFGF), and to analyze the relationship lenalidomide with therapeutic efficacy of leukemia. METHODS: The patients with newly diagnosed acute myeloid leukemia (except M3) from October 2013 to October 2014 in our hospital were randomly divided into 2 groups: chemotherapy+placebo (CP) group and lenalidomide+chemotherapy (LC) group. In addition, healthy persons were used as healthy controls (HC). The expression of VEGF and bFGF was detected by ELISA, and the therapeutic efficacy for AML patients was analyzed. RESULTS: The therapeutic efficacy in LC group and CP group was 87.9% and 77.2% respectively. Before treatment, the VEGF level in LC and CP groups was obviously higher than that in HC group; after treatment, the VEGF level significanthy decreased, and the decreased degree in LC group was larger than that in CP group. Before treatment, the bFGF level in LC and CP groups was higher than that in HC group; after treatment, the bFGF level decreased, and decreased degree in LC group was larger than that in CP group. CONCLUSION: The lenalidomide combined with chemotherapy can significantly decrease the expression level of VEGF and bFGF, and enhance the remission rate of patients with AML.

Meta-analysis of the association of MTHFR polymorphisms with multiple myeloma risk.

The association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with multiple myeloma (MM) risk has been explored, but the results remain controversial. Thus, a meta-analysis was performed to provide a comprehensively estimate. The case-control studies about MTHFR C677T and A1298C polymorphisms with MM risk were collected by searching PubMed, Elsevier, China National Knowledge Infrastructure and Wanfang Databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of association. Overall, no significant association was found between MTHFR A1298C polymorphism and MM risk under all four genetic models (AC vs. AA, OR = 0.99, 95%CI = 0.82-1.20; CC vs. AA, OR = 1.14, 95%CI = 0.77-1.68; recessive model, OR = 1.10, 95%CI = 0.76-1.59; dominant model, OR = 1.01, 95%CI = 0.84-1.22). The risk was also not significantly altered for C677T polymorphism and MM in overall comparisons (CT vs. CC, OR = 1.04, 95%CI = 0.93-1.17; TT vs. CC, OR = 1.16, 95%CI = 0.98-1.37; recessive model, OR = 1.13, 95%CI = 0.98-1.32; dominant model, OR = 1.07, 95%CI = 0.96-1.20). In subgroup analyses by ethnicity, no significant association was observed in both Caucasians and Asians. This meta-analysis suggested that MTHFR polymorphisms were not associated with MM risk.

CYP3A5 ∗ 3 genetic polymorphism is associated with childhood acute lymphoblastic leukemia risk: A meta-analysis.

BACKGROUND: Several studies have investigated the association between CYP3A5 FNx01 3 genetic polymorphism and acute lymphoblastic leukemia (ALL) risk in children, but have yielded controversial results. Therefore, we performed a meta-analysis to evaluate synthetically the effect of CYP3A5 FNx01 3 polymorphism on the risk of ALL in children. METHODS: Case-control studies investigating the relationship between CYP3A5 FNx01 3 genetic polymorphism and ALL risk in children were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of association between CYP3A5 FNx01 3 polymorphism and ALL risk in children. Q-statistic test was used to evaluate the heterogeneity and publication bias was assessed through funnel plot. RESULTS: In total, five case-control studies with 1070 cases and 1125 controls were included in the meta-analysis. Based on the results of heterogeneity, fixed-effects or random-effects models were applied to estimate the pooled ORs. The pooled ORs (95% CIs) for CYP3A5 FNx01 3 heterozygous mutant, homozygous mutant, and (heterozygous + homozygous) mutant were 1.47 (0.97-2.21), 1.05 (0.62-1.79), and 1.67 (1.14-2.44) with P = 0.07, 0.86, and 0.009, respectively. In subgroup analysis, the Z values of CYP3A5 FNx01 3 (heterozygous + homozygous) mutant and children with ALL in Asian and Caucasian populations were 1.34 and 2.51 with P = 0.18 and 0.01, respectively. No significant publication bias was detected by funnel plot. CONCLUSIONS: The current meta-analysis showed that there was association between CYP3A5 FNx01 3 polymorphism and the altered risk of ALL in children, especially in Caucasian populations.

[Effects of COX-2 inhibitor celecoxib on expressions of VEGF, b-FGF and TGF-ß mRNA in acute leukemia cells].

This study was aimed to investigate the influence and significance of celecoxib (specific inhibitor of cyclooxygenase-2) on mRNA expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), transforming growth factor ß (TGF-ß) in acute leukemia cells. The expressions of VEGF, b-FGF, TGF-ß mRNA were measured by RT-PCR in acute leukemia cells treated with celecoxib (80 µmol/L, for 48 h) or with PBS. The results showed that the obvious expressions of VEGF, b-FGF, TGF-ß mRNA were observed in acute leukemia cells. By using Pearson correlation analysis, there was positive correlation between VEGF mRNA and b-FGF mRNA expressions (r = 0.559, P = 0.001), and negative correlation between VEGF and TGF-ß mRNA expressions (r = -0.4, P = 0.029). Expression levels of VEGF, b-FGF, TGF-ß mRNA in experimental group were lower than that in control group (P < 0.01). It is concluded that COX-2 inhibitor celecoxib can inhabit vascular endothelial growth through down-regulating the mRNA expression of VEGF, b-FGF and TGF-ß in acute leukemia cells. COX-2 inhibitor may offer supplemental effect for treating acute leukemia.

[Expression of osteopontin and VEGF in acute leukemia and their relationship with angiogenesis].

The aim of this study was to investigate the expression of osteopontin (OPN) and vascular endothelial growth factor (VEGF) in acute leukemia (AL) and its significance in the angiogenesis and progress of AL. Serum levels of OPN and VEGF in 25 de novo patients, 19 complete remitted (CR) patients, 14 unremitted patients, and 11 relapsed patients with AL were measured by enzyme-linked immunosorbent assay (ELISA), and compared with those in normal controls. The results showed that the serum levels of OPN and VEGF in de novo, unremitted, relapsed patients were significantly higher than those in normal controls and CR patients (p < 0.01). Compared with de novo AL patients group, the serum levels of OPN and VEGF in CR patients decreased significantly, but showed no significant difference from those in normal controls (p > 0.05). The expression of OPN and VEGF in acute leukemia was positively correlated with occurrence and development of AL. It is concluded that the expressions of OPN and VEGF are closely related with AL occurrence and development, the OPN may regulate VEGF expression and promote angiogenesis in acute leukemia. Preventing expressions of OPN may seem as targets for leukemia therapy in the future.

[Expression of angiogenin-2 and VEGF in acute leukemia and its significance].

The aim of study was to investigate the expression of angiogenin-2 (Ang-2) and vascular endothelial growth factor (VEGF) expression in acute leukemia (AL) and its significance in the angiogenesis and progress of AL. Serum levels of Ang-2 and VEGF in 24 de novo, 18 complete remitted (CR), 7 unremitted, 13 relapsed patients with AL were measured by enzyme-linked immunosorbent assay (ELISA), and compared with those of normal controls. The results showed that the serum levels of Ang-2 and VEGF in de novo, unremitted and relapsed patients were significantly higher than those in normal controls (p < 0.01). Compared with de novo group, the serum levels of Ang-2 and VEGF in CR patients decreased significantly, but showing no significant difference from those in normal controls (p > 0.05). In relapsed patients, the serum levels of Ang-2 and VEGF were obviously higher than those in unremitted and CR patients (p < 0.01). It is concluded that the expressions of Ang-2 and VEGF are closely related with occurrence and development of acute leukemia, the VEGF may regulate Ang-2 expression and promote angiogenesis and acute leukemia development. Preventing expressions of Ang-2 and VEGF may seem as targets for leukemia therapy in the future.