The Impact of Novel Molecular Markers on Risk Stratification in Acute Myeloid Leukemia

Abstract SCI-33

The treatment of acute myeloid leukemia (AML) remains associated with considerable failure rates. From a therapy viewpoint AML presents as a kaleidoscope of highly diverse diseases for which the (epi)genetic heterogeneity of the disease is the overriding determinant of treatment failure. Diverse coemerging molecular abnormalities (gene mutations, expression abnormalities) related, for instance, to the genes CEBPA, nucleophosmin-1, FLT-3, RUNX1, ASXL1, P53, G-CSF-R, IDH1/IDH2, DNMT3A, and EVI-1 in variable composite configurations, determine the considerable “interindividual” and “intraindividual” variations of AML. As these somatic genetic abnormalities in transformed hematopoietic progenitor cells perturb critical cellular pathways and functions, they confer a profound impact upon the clinical phenotype of the disease—and also may define unique diagnostic subtypes (diagnosis) and therapeutic resistance (treatment response). Using genome-wide approaches and well-defined cohorts, the identified molecular biomarkers provide insights into the variability of treatment outcome, and furnish an informative framework for risk-adapted treatment decisions according to disease risk and therapeutic responsiveness (prognosis and treatment choice). In this presentation, examples of strategies to assess the prognostic impact of genomic abnormalities will be discussed, as well as the challenge to integrate the numerous markers into meaningful decision algorithms that can be used for more individualized therapy choices, for example, regarding the use of particular therapeutic agents and the utility (risk-benefit) of allogeneic stem cell transplantation.