Analysis Of WT1Mutations And Single Nucleotide Polymorphism RS16754and Clinical Significance In Patients With Pediatric Acute Myeloid Leukemia

Purpose: Acute myelogenous leukemia （AML） is relatively rare inchildren. Somatic mutations and the single nucleotide polymorphism （SNP）rs16754in the Wilms tumor1gene （WT1） and their prognostic relevance inpediatric AML have not been studied in Chinese populations This study wasto analyze WT1mutation frequency in pediatric AML and their prognosticvalue.Method: A total of127de novo AML patients were consecutivelyevaluated by cytogenetic，FISH and molecular analysis detection, thepatients were assigned to different cytogenetic risk categories defined by theSouthwest Oncology Group. We analyzed WT1mutations and rs16754genotypes in a cohort of86AML patients.Result: WT1mutations were detected in approximately20%of thepatients, most of the mutations were deletions and insertions which clusteredin exons7and9. No differences were observed with respect to overallsurvival and relapse-free survival between the patients with and withoutWT1mutations. Analysis of WT1exon7revealed G as the major allele forSNP rs16754. The frequences of rs16754^GGand rs16754^GAwere54.2%and37.5%, respectively. The patients with the rs16754^GGgenotype hadimproved overall survival （p=0.020） and relapse-free survival （p=0.025） compared with those with either rs16754^GAor rs16754^AA. Moreover, betteroverall survival （p=0.068） and relapse-free survival （p=0.044） wereobserved among wild-type CEBPA patients with rs16754^GGcompared withthose carrying rs16754^GA/AA.Discussion: WT1mutations were not shown to have effect on pediatricAML outcome. AML patients with the rs16754^GGgenotype had improvedOS and RFS. This trend was also present among the rs16754^GGpatientswithout CEBPA mutations.