Dissecting the Genetic and Non-Genetic Heterogeneity of Acute Myeloid Leukemia Using Next-Generation Sequencing and In Vivo Models

Abstract

Acute myeloid leukemia (AML) is an extremely aggressive and heterogeneous disorder that results from the transformation of hematopoietic stem cells. Although our understanding of the molecular pathology of AML has greatly improved in the last few decades, the overall and relapse free survival rates among AML patients remain quite poor. This is largely due to evolution of the disease and selection of the fittest, treatment-resistant leukemic clones. There is increasing evidence that most AMLs possess a highly complex clonal architecture and individual leukemias are comprised of genetically, phenotypically and epigenetically distinct clones, which are continually evolving. Advances in sequencing technologies as well as studies using murine AML models have provided further insights into the heterogeneity of leukemias. We will review recent advances in the field of genetic and non-genetic heterogeneity in AML.