The contribution of cell hashing for single-cell analysis of acute leukemia

Abstract

After decades during which the treatment of acute myeloblastic leukemia consisted in cytarabine + anthracycline, targeted therapies have appeared, first based on monoclonal antibodies (anti-CD52, anti-CD123) and then on specific inhibitors of molecular mutations (anti-IDH, IDH2 or FLT3). What should be the place of these therapeutic options considering the tumor heterogeneity inherent to leukemia diagnosis and the clonal drift of which this type of tumor is capable? Targeted drugs would require an analysis of the various therapeutic targets not in the total population but at the individual cell level. Indeed, the prognostic value and therapeutic interest of a given molecular target are certainly not the same if it is a cell in terminal differentiation with low proliferative potential or, on the contrary, a stem cell with strong capacities of both proliferation and self-renewal. However, this cell-by-cell analysis is fraught with several pitfalls. The first one is scientific because the comparison of two different single cell analysis experiments is delicate, in spite of the different techniques aiming at standardizing the results. The second pitfall is practical, as each single cell experiment is very costly from a financial point of view but also very time consuming. The solution is therefore to be able to process several samples at the same time, which is the specificity of the cell hashing technique. In this study we demonstrate that the cell hashing technique can be used for the analysis of acute myeloid leukemia cells. We compared the cell hashing technique with the classic single cell analysis and demonstrated a good concordance of different parameters: quality control, gene expression correlation, expression analysis of leukemic blast markers in both patients. The technique could thus in the future be part of the biological assessment of acute myeloid leukemia and contribute to the individualization and optimization of their management, particularly in the context of the use of targeted therapies.