Biomarkers in acute myeloid leukemia: From state of the art in risk classification to future challenges of RNA editing as disease predictor and therapy target

Acute Myeloid Leukemia (AML) is currently diagnosed based on morphological assessment of myeloid cells’ features, immunophenotypic characterization of specific cell surface and intracellular markers, conventional cytogenetic testing and screening for genetic abnormalities in bone marrow and peripheral blood specimens. In recent years new technologies have shed light on the complexity and heterogeneity of this elusive leukemia and are providing useful biomarkers, predictive of prognosis in AML patients. Hence, technological efforts are being made in order to identify more accurate AML biomarkers also useful to track minimal residual disease at the various follow-up times. This remains an unmet need that, together with the intrinsic tumor features of AML, results in the highest death rate of all leukemias and a 5-year overall survival <50%. This review provides insights into the state-of-the-art of AML-related biomarkers and their role in clinical practice as prognostic indicators, minimal residual disease detection or candidates for targeted therapy. In addition, we report modifications of RNA epitranscriptome during normal hematopoiesis that are de-regulated in AML, recently revealed by new and more sophisticated techniques. We focus on alterations of m⁶A modifications on mRNAs and of enzymes catalyzing them, which have been reported to affect normal hematopoiesis and leukemogenesis and are providing novel promising biomarkers for AML risk assessment and newly druggable targets for treatment.