Objective:Intermediate-risk acute myeloid leukemia (IR-AML),which accounts for a substantial number of AML cases,is highly heterogeneous.We systematically summarize the latest research progress on the significance ofgene mutations for prognostic stratification of IR-AML.Data Sources:We conducted a systemic search from the PubMed database up to October,2014 using various search terms and their combinations including IR-AML,gene mutations,mutational analysis,prognosis,risk stratification,next generation sequencing (NGS).Study Selection:Clinical or basic research articles on NGS and the prognosis of gene mutations in IR-AML were included.Results:The advent of the era of whole-genome sequencing has led to the discovery of an increasing number of molecular genetics aberrations that involved in leukemogenesis,and some of them have been used for prognostic risk stratification.Several studies have consistently identified that some gene mutations have prognostic relevance,however,there are still many controversies for some genes because of lacking sufficient evidence.In addition,tumor cells harbor hundreds of mutated genes and multiple mutations often coexist,therefore,single mutational analysis is not sufficient to make accurate prognostic predictions.The comprehensive analysis of multiple mutations based on sophisticated genomic technologies has raised increasing interest in recent years.Conclusions:NGS represents a pioneering and helpful approach to prognostic risk stratification of IR-AML patients.Further large-scale studies for comprehensive molecular analysis are needed to provide guidance and a theoretical basis for IR-AML prognostic stratification and clinical management.