Clonally resolved single-cell multi-omics identifies routes of cellular differentiation in acute myeloid leukemia

• DOI: 10.1016/j.stem.2023.04.001
• Publication Date: 2023-04-24T14:41:20Z
• Authors: Sergi Beneyto-Cal...; Anne Kathrin Merbach; Jonas-Alexander K...; Magdalena Antes; Chelsea Szu-Tu; Christian Rohde; Alexander Waclawi...; Patrick Stelmach; Sarah Gräßle; Philip Pervan; Maike Janssen; Jonathan J.M. Landry; Vladimir Benes; Anna Jauch; Michaela Brough; Marcus Bauer; Birgit Besenbeck; Julia Felden; Sebastian Bäumer; Michael Hundemer; Tim Sauer; Caroline Pabst; Claudia Wickenhauser; Linus Angenendt; Christoph Schliemann; Andreas Trumpp; Simon Haas; Michael Scherer; Simon Raffel; Carsten Müller-Tidow; Lars Velten
• Keywords: Compartment (ship)

Inter-patient variability and the similarity of healthy leukemic stem cells (LSCs) have impeded characterization LSCs in acute myeloid leukemia (AML) their differentiation landscape. Here, we introduce CloneTracer, a novel method that adds clonal resolution to single-cell RNA-seq datasets. Applied samples from 19 AML patients, CloneTracer revealed routes differentiation. Although residual preleukemic dominated dormant cell compartment, active resembled counterpart retained erythroid capacity. By contrast, downstream progenitors constituted highly aberrant, disease-defining compartment: gene expression state affected both chemotherapy response leukemia's ability differentiate into transcriptomically normal monocytes. Finally, demonstrated potential identify surface markers misregulated specifically cells. Taken together, reveals landscape mimics its may determine biology therapy AML.