Final Destination: Distinct Cell Differentiation Patterns in Acute Myeloid Leukemia Revealed

Rebecca Roberts in The Scientist:

In a presentation at the American Association for Cancer Research (AACR) Annual Meeting 2025, author Andy Zeng of the University of Toronto revealed that their approach could distinguish 12 distinct patterns of differentiation across AML samples—this level of granular information could not be achieved using current methods. “You can see that despite having the same diagnosis, they differ profoundly in terms of the regions of hematopoiesis that are implicated,” said Zeng. The team used their reference map for normal hematopoiesis, comprised of 263,159 single-cell transcriptomes across 55 cell states, as a North Star. They mapped over 1.2 million cells from more than 300 leukemia samples to this reference atlas to determine patterns of aberrant differentiation.

Among the different cell differentiation stages that the team identified, some were characterized by early blocks in differentiation, and some by the enrichment of differentiation states from many stages of hematopoiesis. Others were characterized by the enrichment of differentiation states from a specific progenitor, such as an erythroid, lymphoid, or myeloid progenitor. Erythroid and lymphoid enrichment were unexpected because AML is typically characterized by a differentiation trajectory toward myeloid cells.

More here.

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