Characterization of acute erythroid leukemia using mass cytometry
Abstract
Acute erythroleukemia (AEL) is a rare subtype of acute myeloid leukemia (AML) which accounts for less than 5% of all de novo AML cases. There have been several efforts to characterize AEL at a molecular level, describing recurrent alterations in TP53 and in the NPM1 and FLT3 gene (Iacobucci et al. Nat Genet 2019). A comprehensive genomic analysis of AEL cases confirmed the complexity of this AML subtype. Despite these advances, the underlying biology of AEL is still not precisely defined and the prognosis is dismal with a median survival of only 2-3 months for pure erythroid leukemia. Marker combinations suitable for 1) the identification and characterization of leukemic stem cell (LSC) candidates, 2) monitoring minimal residual disease during chemotherapy treatment and 3) the development of innovative targeted therapies are missing. Along with a comprehensive multiomics approach, flow cytometry and murine bone marrow transplantation experiments, we developed a mass cytometry marker panel for an in-depth characterization of human AEL bone marrow samples in comparison to other AML subtypes and bone marrow (BM) from healthy donors. A total of 8 AELs, 30 AMLs and 5 BM controls were successfully analyzed. Marker combinations, identified and validated by conventional flow cytometric analysis, were able to separate erythroid from myeloid blast populations and might help in identifying MRD.
Biosketch
Habib Rahimi is currently a PhD Student at the Institute of Experimental Cancer Research and the International Graduate School in Molecular Medicine in Ulm, Germany. His research mainly focuses on acute myeloid leukemia, hematopoietic stem cells and aging. He is a member of the Cellular and Molecular Mechanisms in Aging (CEMMA)-research group (GRK 1789) and is involved in projects within the CRC Experimental Models and Clinical Translation in Leukemia (SFB 1074) and the Aging-related epigenetic remodeling in acute myeloid leukemia consortium (FOR 2674).
Keywords
Acute erythroleukemia (AEL), Minimal residual disease (MRD), Leukemic stem cells (LSC)
Contact
E-mail: abdul-habib.rahimi@uni-ulm.de
Links
Institute of experimental cancer research University Hospital Ulm