The cellular state space of AML unveils novel NPM1 subtypes with distinct clinical outcomes and immune evasion properties

Acute myeloid leukemia (AML) is a genetically and cellularly heterogeneous disease. We characterized 120 AMLs using bulk genomic and transcriptomic analyses (WES, MP-WGS, RNA-seq), and single-cell RNA sequencing (scRNA-seq). Our results reveal an extensive cellular heterogeneity that distorts the bulk transcriptomic profiles. Notably, NPM1 mutated AML could be stratified into two novel, clinically relevant classes (NPM1class I and NPM1class II).

Type: Transcriptome Analysis
Archiver: Federated European Genome-Phenome Archive (FEGA Sweden)

4 Datasets 2 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD50000001574	This dataset contains bam-files from Mate-pair whole genome sequencing of 98 AML samples. DNA was extracted from either bone marow or peripheral blood from primary AML samples. The libraries were prepared using Illumina Nextera mate pair library preparation kit, generating long-insert (2-8 kb) paired end libraries. These were sequenced on an Illumina NextSeq 500 using 2x76bp paired end chemistry. The fastq files generated by sequencing were aligned to the human hg19 reference genome (ucsc.hg19.fasta from the GATK resource bundle) using bwa (0.7.15-r1140) and duplicate reads were identified using samblaster (0.1.24).	NextSeq 500	98
EGAD50000001575	This dataset contains bam-files from whole exome sequencing of 120 paired tumor-normal pairs from AML. Tumor DNA was extracted from either bone marow or peripheral blood from primary AML samples. Normal DNA was extracted from cultured skin fibroblast samples. The libraries were prepared using the Nextera rapid capture exome kit and sequenced on an Illumina NextSeq 500 using 2x151bp paired end chemistry. The fastq files generated by sequencing were aligned to the human hg19 reference genome (ucsc.hg19.fasta from the GATK resource bundle) using bwa (0.7.9a-r786 or 0.7.15-r1140) and duplicate reads were identified using samblaster (0.1.24).	NextSeq 500	232
EGAD50000001576	This dataset contains fastq-files from bulk RNA sequencing of 120 AML samples. RNA was extracted from either bone marow or peripheral blood from primary AML samples. The libraries were prepared using Illumina Truseq RNA library preparation kit v2 and sequenced on an Illumina NextSeq 500 using 2x151bp paired end chemistry.	NextSeq 500	120
EGAD50000001577	This dataset contains fastq-files from single cell 3' RNA- and feature barcode sequencing of AML samples using 10X technology (Chromium Single Cell 3ʹ Reagent Kit v3). In total, the dataset contains data from 38 AML samples from either bone marrow or peripheral blood, representing the following genetic subtypes: NPM1-mutated, myelodysplasia related, TP53-mutated, CBFB::MYH11, RUNX1::RUNX1T1, AML without class-defining mutations, and AML meeting criteria of two subtypes. The data consists of sequenced gene expression libraries from 38 samples and feature barcoding libraries covering a panel of 10-14 surface proteins for 34 samples.	unspecified	72

Publications	Citations
Aberrant expression of SLAMF6 constitutes a targetable immune escape mechanism in acute myeloid leukemia. Sandén C, Landberg N, Peña-Martínez P, Thorsson H, Daga S, Puente-Moncada N, Rodriguez-Zabala M, von Palffy S, Rissler M, Lazarevic V, Juliusson G, Ohlin M, Hyrenius-Wittsten A, Orsmark-Pietras C, Lilljebjörn H, Ågerstam H, Fioretos T. Nat Cancer 6: 2025 1821-1838	0
The AML cellular state space unveils NPM1 immune evasion subtypes with distinct clinical outcomes. Lilljebjörn H, Peña-Martínez P, Thorsson H, Henningsson R, Rissler M, Landberg N, Puente-Moncada N, von Palffy S, Rissler V, Stanek P, Desponds J, Zhong X, Juliusson G, Lazarevic V, Lehmann S, Fontes M, Ågerstam H, Sandén C, Orsmark-Pietras C, Fioretos T. Nat Commun 16: 2025 10592	1