Systematic Multi-Parametric Analysis of Acute Myeloid Leukemia (AML) Flow Cytometry Drug Screens using Flowty

Abstract: Acute myeloid leukemia (AML) is a heterogeneous disease, making it difficult to treat. The standard treatment is intensive chemotherapy and has not changed in 40 years. However, recently new drugs and as less intensive treatment regimens have been approved in the US and in Europe. However. With a larger therapeutic toolbox, there is an urgent need for predictive biomarkers to offer the optimal treatment for the patient, also referred to as precision medicine. This project investigated AML flow cytometry drug screens using the unpublished analytical application, Flowty. Cellular subpopulations present in AML bone marrow samples were visualized based on their phenotypic expression of the biomarkers CD34, CD38, CD33, CD45, CD64, CD117 and HLA-DR, as well as granularity. This enabled investigation of whether AML patients and subpopulations with similar differentiation phenotypes have similar drug response. The aim was to explore the possibility of using differentiation phenotype to dictate on AML precision medicine. The heterogeneity in drug response was evident when comparing patients. However, exploring a small patient cohort, subpopulations with similar phenotypic expression demonstrated a similar drug response across patients. Furthermore, future aspects of research were proposed, focusing on additional analysis of the correlations between phenotypic expression and drug response.