Esculetin downregulates the expression of AML1-ETO and C-Kit in Kasumi-1 cell line by decreasing half-life of mRNA

One of the most frequent genetic aberrations in acute myeloid leukemia (aml) is chromosomal translocation between aml1/runx1 on chromosome 21 and eto gene on chromosome 8 resulting in the expression of chimeric oncogene aml1-eto. although patients with t(8;21) translocation have good prognosis,5-year survival is observed only in 50% of the cases. aml1-eto translocation is usually accompanied by overexpression of mutant c-kit,a tyrosine kinase,which contributes to uncontrolled proliferation of premature blood cells leading to relapse and poor prognosis. we illustrate the potential use of esculetin on leukemic cell line,kasumi-1,bearing t(8;21) translocation and mutated c-kit gene. esculetin decreases the expression of aml1-eto at both protein and transcript level within 24 hours of treatment. half-life of aml1-eto mrna was reduced from 7 hours to 1.5 hours. similarly half-life of c-kit mrna was reduced to 2 hours from 5 hours in esculetin treated cells. esculetin also perturbed the expression of ectopically expressed aml1-eto in u937 cells. the decreased expression of aml1-eto chimeric gene was associated with increased expression of lat1 and runx3 genes,targets of aml1. we envisage that discovery of a drug candidate which could target both these mutated genes would be a considerable breakthrough for future application. © 2015 sharad sawney et al.