Acute Myeloid Leukemia: The Challenge of Capturing Disease Variety

Fifty years ago when the American Society of Hematology was founded, the diagnosis of AML was based solely on microscopic evaluation. It was considered one monolithic disease for which “one size fits all” chemotherapy was available. Recent therapeutic and diagnostic developments have created a realistic perspective of personalized therapeutics in AML. Numerous genetic abnormalities (i.e., cytogenetics, gene mutations, and expression abnormalities) have meanwhile been discovered. Examples of clinically relevant gene aberrations involve CEBP-alpha, RAS, nucleophosmin-1, FLT-3, WT1, EVI-1, MN-1, and ERG, but there may be more to come. The remarkable heterogeneity is a reflection of the underlying somatic genetic abnormalities in transformed hematopoietic stem cells that, as successive events over years, have accumulated in the neoplastic clone of a patient’s leukemia during the evolution of the disease. As these genetic changes perturb diverse cellular pathways and functions, they may confer a profound impact upon the clinical phenotype of the disease and treatment response. In this presentation, I will review recent insights into the prognostic impact of chromosomal abnormalities and genomic abnormalities, highlight the relationship of microRNA patterns to the clinical variability of AML, and discuss the abilities to construct decision algorithms for individualized therapies, such as targeted drugs and allogeneic stem cell transplantation.