220: AML cell states reveal NPM1 immune-evasion subtypes

Lilljebjörn H et al., Nat Commun - Single-cell and bulk sequencing of 120 AML cases reveal two NPM1-mutated subtypes with distinct immune evasion mechanisms and divergent responses to hematopoietic stem cell transplantation. Key terms: acute myeloid leukemia, single-cell RNA-seq, NPM1, immune evasion, hematopoietic stem cell transplantation. Study Highlights:Bulk RNA-seq profiles are strongly confounded by variable mature cell-type signatures that can conceal subtype-specific blast programs. Single-cell multimodal sequencing of AML identified four main clusters of immature leukemic cells and separated NPM1-mutated cases into NPM1class I and NPM1class II. NPM1class I is marked by MHC class II downregulation and shows a significant survival benefit from HSCT, while NPM1class II resists allogeneic T cell killing ex vivo and does not benefit from HSCT. A 180-gene signature, and a shorter 30-gene panel, distinguished the classes across external bulk cohorts and associated each subtype with different co-mutation patterns. Conclusion:Single-cell transcriptional profiling defines two clinically relevant NPM1 subtypes with distinct immune evasion strategies that may inform HSCT decisions and immunotherapy approaches. Music:Enjoy the music based on this article at the end of the episode. First author:Lilljebjörn H Journal:Nature Communications DOI:10.1038/s41467-025-66546-6 Reference:Lilljebjörn H, Henningsson R, Rissler M, Landberg N, Puente-Moncada N, von Palffy S, Rissler V, Stanek P, Desponds J, Lazarevic V, Lehmann S, Fontes M, Ågerstam H, Sandén C, Orsmark-Pietras C, Zhong X, Juliusson G, Thorsson H, Fioretos T. The AML cellular state space unveils NPM1 immune evasion subtypes with distinct clinical outcomes. Nat Commun. 2025;16:10592. https://doi.org/10.1038/s41467-025-66546-6 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/npm1-immune-evasion-subtypes ️ Episode:220: The AML cellular state space reveals NPM1 immune evasion subtypes ️ Season:1 Article title:The AML cellular state space unveils NPM1 immune evasion subtypes with distinct clinical outcomes QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-12-06. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited the transcript sections describing AML heterogeneity, single-cell sequencing approaches, isolation of AML immature cells, the NPM1 class I/II dichotomy, MHC-II downregulation and CIITA, intrinsic T cell resistance, ex vivo T cell assays, HSCT outcomes, and the minimal 30-gene panel for clinical implementation.- transcript topics: AML heterogeneity and leukemia stem cells; Single-cell multimodal sequencing (scRNA-seq + scADT-seq); Isolation and characterization of AML immature cells; NPM1-mutated AML: NPM1 class I and NPM1 class II; MHC class II downregulation and CIITA regulation; Intrinsic T cell resistance and alternative checkpoint pathways QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 6- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal