Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

The AML cellular state space unveils NPM1 immune evasion subtypes with distinct clinical outcomes

Lilljebjörn, Henrik LU orcid ; Peña-Martínez, Pablo LU ; Thorsson, Hanna LU ; Henningsson, Rasmus LU ; Rissler, Marianne LU ; Landberg, Niklas LU orcid ; Puente-Moncada, Noelia LU ; von Palffy, Sofia LU ; Rissler, Vendela LU and Stanek, Petr LU , et al. (2025) In Nature Communications 16. p.1-16
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 NPM1class I associated with downregulation of MHC class II and excellent survival following hematopoietic stem cell transplantation. NPM1class II is instead associated with resistance to... (More)

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 NPM1class I associated with downregulation of MHC class II and excellent survival following hematopoietic stem cell transplantation. NPM1class II 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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Nucleophosmin, Leukemia, Myeloid, Acute/genetics, Nuclear Proteins/genetics, Female, Mutation, Male, Hematopoietic Stem Cell Transplantation, Middle Aged, Single-Cell Analysis, Adult, Transcriptome, Gene Expression Profiling, Aged, Immune Evasion/genetics, T-Lymphocytes/immunology
in
Nature Communications
volume
16
article number
10592
pages
1 - 16
publisher
Nature Publishing Group
external identifiers
  • pmid:41290664
  • scopus:105023127342
ISSN
2041-1723
DOI
10.1038/s41467-025-66546-6
language
English
LU publication?
yes
additional info
© 2025. The Author(s).
id
a8e111de-97ff-4077-b670-830aeb303c0f
date added to LUP
2025-12-04 07:23:16
date last changed
2025-12-05 04:01:16
@article{a8e111de-97ff-4077-b670-830aeb303c0f,
  abstract     = {{<p>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 &gt;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 NPM1class I associated with downregulation of MHC class II and excellent survival following hematopoietic stem cell transplantation. NPM1class II 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.</p>}},
  author       = {{Lilljebjörn, Henrik and Peña-Martínez, Pablo and Thorsson, Hanna and Henningsson, Rasmus and Rissler, Marianne and Landberg, Niklas and Puente-Moncada, Noelia and von Palffy, Sofia and Rissler, Vendela and Stanek, Petr and Desponds, Jonathan and Zhong, Xiangfu and Juliusson, Gunnar and Lazarevic, Vladimir and Lehmann, Sören and Fontes, Magnus and Ågerstam, Helena and Sandén, Carl and Orsmark-Pietras, Christina and Fioretos, Thoas}},
  issn         = {{2041-1723}},
  keywords     = {{Humans; Nucleophosmin; Leukemia, Myeloid, Acute/genetics; Nuclear Proteins/genetics; Female; Mutation; Male; Hematopoietic Stem Cell Transplantation; Middle Aged; Single-Cell Analysis; Adult; Transcriptome; Gene Expression Profiling; Aged; Immune Evasion/genetics; T-Lymphocytes/immunology}},
  language     = {{eng}},
  month        = {{11}},
  pages        = {{1--16}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{The AML cellular state space unveils NPM1 immune evasion subtypes with distinct clinical outcomes}},
  url          = {{http://dx.doi.org/10.1038/s41467-025-66546-6}},
  doi          = {{10.1038/s41467-025-66546-6}},
  volume       = {{16}},
  year         = {{2025}},
}