220: The AML cellular state space reveals NPM1 immune evasion subtypes

️Episode 220: The AML cellular state space reveals NPM1 immune evasion subtypes In this episode of PaperCast Base by Base, we explore 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 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. 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 Castos player https://basebybase.castos.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

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