Details

Autor(en) / Beteiligte

• Beneyto-Calabuig, Sergi
• Merbach, Anne Kathrin
• Kniffka, Jonas-Alexander
• Antes, Magdalena
• Szu-Tu, Chelsea
• Rohde, Christian
• Waclawiczek, Alexander
• Stelmach, Patrick
• Gräßle, Sarah
• Pervan, Philip
• Janssen, Maike
• Landry, Jonathan J.M.
• Benes, Vladimir
• Jauch, Anna
• Brough, Michaela
• Bauer, Marcus
• Besenbeck, Birgit
• Felden, Julia
• Bäumer, Sebastian
• Hundemer, Michael
• Sauer, Tim
• Pabst, Caroline
• Wickenhauser, Claudia
• Angenendt, Linus
• Schliemann, Christoph
• Trumpp, Andreas
• Haas, Simon
• Scherer, Michael
• Raffel, Simon
• Müller-Tidow, Carsten
• Velten, Lars

Titel

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

Ist Teil von

• Cell stem cell, 2023-05, Vol.30 (5), p.706-721.e8

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Inter-patient variability and the similarity of healthy and leukemic stem cells (LSCs) have impeded the characterization of LSCs in acute myeloid leukemia (AML) and their differentiation landscape. Here, we introduce CloneTracer, a novel method that adds clonal resolution to single-cell RNA-seq datasets. Applied to samples from 19 AML patients, CloneTracer revealed routes of leukemic differentiation. Although residual healthy and preleukemic cells dominated the dormant stem cell compartment, active LSCs resembled their healthy counterpart and retained erythroid capacity. By contrast, downstream myeloid progenitors constituted a highly aberrant, disease-defining compartment: their gene expression and differentiation state affected both the chemotherapy response and leukemia’s ability to differentiate into transcriptomically normal monocytes. Finally, we demonstrated the potential of CloneTracer to identify surface markers misregulated specifically in leukemic cells. Taken together, CloneTracer reveals a differentiation landscape that mimics its healthy counterpart and may determine biology and therapy response in AML. [Display omitted] •CloneTracer extracts clonal information from single-cell RNA-seq data•Data resource of healthy and leukemic stem and progenitor cells from 19 AML cases•Dormant hematopoietic stem cells in AML patients are healthy or preleukemic•Leukemic stem cells resemble active HSCs but form aberrant myeloid progenitors Velten and colleagues develop CloneTracer, a computational method to identify clones in single-cell RNA-seq data. Applied to immature cells from 19 acute myeloid leukemia patients, CloneTracer shows that dormant hematopoietic stem cells (HSCs) are healthy or preleukemic. Leukemic stem cells resemble healthy active HSCs but give rise to aberrant progenitors.