The AML cellular state space unveils NPM1 immune evasion subtypes with distinct clinical outcomes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41290664.
- Also identified by DOI 10.1038/s41467-025-66546-6 and PMC identifier 12658069.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Acute myeloid leukemia is a genetically and cellularly heterogeneous disease. We characterize 120 AMLs using genomic and transcriptomic analyses, including single-cell RNA sequencing. Our results reveal an extensive cellular heterogeneity that distorts the bulk transcriptomic profiles. Selective examination of the transcriptional signatures of >90,000 immature AML cells identifies four main clusters, thereby extending current genomic classification of AML. Notably, NPM1-mutated AML can be stratified into two clinically relevant classes, with NPM1<sup>class I</sup> associated with downregulation of MHC class II and excellent survival following hematopoietic stem cell transplantation. NPM1<sup>class II</sup> is instead associated with resistance to allogeneic T cells in an ex vivo co-culture assay, and importantly, dismal survival following hematopoietic stem cell transplantation. These findings provide insights into the cellular state space of AML, define diagnostic entities, and highlight potential therapeutic intervention points.
Medical subject headings
- Leukemia, Myeloid, Acute
- Nuclear Proteins
- Immune Evasion