Prognostic significance of cytokine receptor-like factor 2 alterations in acute lymphoblastic leukemia:a meta-analysis

Background:Cytokine receptor-like factor 2(CRLF2)has been shown to play a role in the pathogenesis of acute lymphoblastic leukemia(ALL).Studies have examined the relationship between CRLF2 alterations such as over-expression or deregulation and clinical outcome in childhood ALL,but the results are conflicting.This meta­analysis aimed to explore the association between CRLF2 alterations and survival of pediatric patients with ALL.Methods:Electronic databases updated to March 2014 were searched for relevant studies.A meta-analysis was made of twelve studies including 5945 patients to evaluate the prognostic significance of CRLF2 alterations on survival in childhood ALL.Hazards ratios(HRs)with 95%confidence intervals(CIs)were pooled across the studies using a fixed-effects model.Results:CRLF2 over-expression in childhood ALL was associated with poor prognosis in terms of relapse-free survival(RFS;HR=1.70,95%CI=1.28-2.24,P=0.000),event-free survival(EFS;HR=1.78,95%CI=1.05-3.01,R=0.032),and overall survival(OS;HR=2.28,95%CI=1.42-3.65,R=0.001).The combined data also suggested that CRLF2 deregulation in childhood ALL was correlated with poor EFS(HR=1.95,95%CI=1.46-2.61,R=0.000),RFS(HR=2.20,95%CI=1.53-3.18,P=0.000),and OS(HR=1.89,95%CI=1.24-2.87,P=0.003).Subgroup analysis on multivariate HRs showed that CRLF2 deregulation independently predicted a poor prognosis for childhood ALL.Conclusions:The present meta-analysis reveals that both CRLF2 over-expression and deregulation are associated with poor prognosis in pediatric patients with ALL.