ASH 2021 | Reconstructing clonal evolution from dysplasia to AML

Recognizing the mechanisms of leukemogenesis is important for the development of new therapies that interfere with the tumor evolutionary process in acute myeloid leukemia (AML). Clonal evolution is a long and highly complex process that, at present, cannot be easily investigated in basic laboratory settings. Bruno Paiva, PhD, University of Navarra, Pamplona, Spain, shares a potential new strategy to reconstruct leukemogenesis using readily available techniques. The method is based on the presence of dysplasia. By analyzing residual dysplastic cells that were produced prior to leukemic transformation and comparing their genetic signature to that of leukemic blasts, the evolutionary changes could be revealed. Dysplastic cells were detected in nearly 90% of the 283 patients with newly diagnosed AML, demonstrating the broad applicability of the methodology. Integrated multidimensional flow cytometry and next-generation sequencing revealed three patterns of leukemogenesis: stable transition, clonal selection, and clonal evolution. Dr Paiva discusses these patterns and how they were seen to co-exist. Using this method may enable the identification of genetic drivers of transformation and resistance in an everyday clinical setting. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.