articleBlood Cancer DiscoveryApr 28, 2025HYBRID OA

Single-cell Transcriptional Atlas of Human Hematopoiesis Reveals Genetic and Hierarchy-Based Determinants of Aberrant AML Differentiation

AGAndy G.X. ZengIIIlaria IacobucciSSSayyam ShahAMAmanda MitchellGWGordon Wong

University Health Network · University of Toronto · +4 more institutions

PubMed
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Abstract

Therapeutic targeting of acute myeloid leukemia (AML) is hampered by intra- and inter-tumoral cell state heterogeneity. To develop a more precise understanding of AML cell states, we constructed a reference atlas of human hematopoiesis from 263,159 single-cell transcriptomes spanning 55 cellular states. Using this atlas, we mapped more than 1.2 million cells spanning 318 leukemia samples, revealing 12 recurrent patterns of aberrant differentiation in AML. Notably, this uncovered unexpected AML cell states resembling lymphoid and erythroid progenitors that were prognostic within the clinically heterogeneous context of normal karyotype AML, independent of genomic classifications. Systematic mapping of…

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Topics & keywords

Topics
Keywords
  • Atlas (anatomy)
  • Haematopoiesis
  • Biology
  • Hierarchy
  • Genetics
  • Computational biology
  • Evolutionary biology
  • Stem cell
UN Sustainable Development Goals
  • Good health and well-being
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