| Title: |
Single-cell atlas of AML reveals age-related gene regulatory networks in t(8;21) AML |
| Authors: |
Whittle, Jessica; Meyer, Stefan; Lacaud, Georges; Murtuza-Baker, Syed; Iqbal, Mudassar |
| Source: |
eLife ; volume 14 ; ISSN 2050-084X |
| Publisher Information: |
eLife Sciences Publications, Ltd |
| Publication Year: |
2026 |
| Collection: |
eLife (E-Journal - via CrossRef) |
| Description: |
Acute myeloid leukemia (AML) is characterized by cellular and genetic heterogeneity, which correlates with clinical course. Although single-cell RNA sequencing (scRNA-seq) reflects this diversity to some extent, the low sample numbers in individual studies limit the analytic potential when comparing specific patient groups. We performed large-scale integration of published scRNA-seq datasets to create a unique single-cell transcriptomic atlas for AML (AML scAtlas), totaling 748,679 cells, from 159 AML patients and 51 healthy donors from 20 different studies. This is the largest single-cell data resource for human AML to our knowledge, publicly available at https://cellxgene.cziscience.com/collections/071b706a-7ea7-47a4-bddf-6457725839fc . This AML scAtlas allowed investigations into 20 patients with t(8;21) AML, where we explored the clinical importance of age, given the in-utero origin of pediatric disease. We uncovered age-associated gene regulatory network (GRN) signatures, which we validated using bulk RNA sequencing data to delineate distinct groups with divergent biological characteristics. Furthermore, using an additional multiomic dataset (scRNA-seq and scATAC-seq), we validated our initial findings and created a de-noised enhancer-driven GRN reflecting the previously defined age-related signatures. Applying integrated data analysis of the AML scAtlas, we reveal age-dependent gene regulation in t(8;21) AML, potentially reflecting immature/fetal HSC origin in prenatal origin disease vs postnatal origin. Our analysis revealed that BCLAF1, which is particularly enriched in pediatric AML with t(8;21) of inferred in-utero origin, is a promising prognostic indicator. The AML scAtlas provides a powerful resource to investigate molecular mechanisms underlying different AML subtypes. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.7554/elife.104978.3 |
| Availability: |
https://doi.org/10.7554/elife.104978.3; https://cdn.elifesciences.org/articles/104978/elife-104978-v1.pdf; https://cdn.elifesciences.org/articles/104978/elife-104978-v1.xml; https://elifesciences.org/articles/104978 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.9558584C |
| Database: |
BASE |