Clonal genetic evolution at relapse of favorable-risk acute myeloid leukemia with NPM1 mutation is associated with phenotypic changes and worse outcomes

Abstract

Acute myeloid leukemia (AML) is a dynamic disease caused by accumulating somatically acquired driver mutations generating branching competing clones1. In favorable-risk-AML, high resolution genomic profiling by single-nucleotidepolymorphism- array of paired diagnosis-relapse NPM1mut and CBF AML samples has revealed increased genomic complexity at relapse but most patients retained founding mutations2,3. Furthermore, it has been extensively reported that phenotypic changes are commonly found at relapse in AML patients. It seems plausible that clonal evolution could be also reflected in the phenotypic-shifts of AML blast cells found at relapse, although the correlation with genetic clonal evolution has not been established2,4-7. The aim of our work in to determinate the patterns of genetic clonal evolution occurring from diagnosis to relapse in favorable-risk-AML-patients by tracking the kinetic behavior of most frequent co-mutations in paired samples and correlated with the occurrence of phenotype-shifts on blast cells and with the clinical outcome.