Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution.

"raw single-cell genotyping sequencing data from this study are deposited at the sequence reads achieve (sra; https://www ncbi nlm nih gov/sra ) under the accession number prjna930152 .; raw and processed (counts matrix) single-cell rna-sequencing data from this study are deposited at the gene expression omnibus (geo; https://www ncbi nlm nih gov/geo/ ) under the accession number gse226340 . processed single-cell genotyping data is available at https://zenodo org/record/8060602 (10 5281/zenodo 8060602) (metadata_mpnamlp53_with_index_genotype revised txt; columns 'genotype_curated' 'genotype_labels' and 'genotype classification').; raw and processed snp array data are available at https://zenodo org/record/8073857 (10 5281/zenodo 8073857).; code availability scripts to reproduce data preprocessing and all figures are available on github ( https://github com/albarmeira/p53-transformation ) and source data to reproduce the scripts is available at: https://zenodo org/record/8038152 (10 5281/zenodo 8038152; data preprocessing) and https://zenodo org/record/8060602 (10 5281/zenodo 8060602; source data for figures). code availability scripts to reproduce data preprocessing and all figures are available on github ( https://github com/albarmeira/p53-transformation ) and source data to reproduce the scripts is available at: https://zenodo org/record/8038152 (10 5281/zenodo 8038152; data preprocessing) and https://zenodo org/record/8060602 (10 5281/zenodo 8060602; source data for figures). data availability subsets of the single-cell genotyping and rna-sequencing data were part of a previous study 16 ( gse105454"

"code availability scripts to reproduce data preprocessing and all figures are available on github ( https://github com/albarmeira/p53-transformation ) and source data to reproduce the scripts is available at: https://zenodo org/record/8038152 (10 5281/zenodo 8038152; data preprocessing) and https://zenodo org/record/8060602 (10 5281/zenodo 8060602; source data for figures)."

"Competing interests A.R.M. and A.J.M. are authors on a patent related to TARGET-seq (US Patent App. 17/038,548). A patent relating to the TARGET-seq technique is licensed to Alethiomics, a spin-out company from the University of Oxford with equity owned by B.P. and A.J.M. and research funding to B.P. and A.J.M. The other authors declare no competing interests."

"We are grateful to patients and donors as without their generosity, this study would not have been possible. We also thank S. Knapper, clinical study teams and other investigators involved in supporting sample collection, and King’s Health Partners Biobank for providing access to samples. We thank Z. Ren, T. Denaes and H. Duparc for their help with mouse experiments and S.-A. Clark for help with sorting. We also thank C. Soblechero for the help with computational analysis. This work was funded by a Medical Research Council (MRC) Senior Clinical Fellowship (MR/L006340/1 to A.J.M.), CRUK Senior Cancer Research Fellowship (C42639/A26988 to A.J.M.), Cancer Research UK (CRUK) DPhil Prize Studentship (C5255/A20936 to A.R.-M.), Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust (222800/Z/21/Z to A.R.-M.), British Spanish Society Scholarship (to A.R.-M.), MRC Confidence in Concept/MLSTF Grant (MC_PC_19049 to A.R.-M. and A.J.M.), the MRC Molecular Haematology Unit core award (MC_UU_12009/5 to A.J.M. and S.E.W.J.), Emergence Cancéropôle Ile de France 2017 (to I.A.-D.), Association pour la Recherche contre le Cancer 2018 (to I.A.-D.), Gustave Roussy Siric-Socrate 2019 (to I.A.-D.), Institut National du Cancer INCA-PLBIO 2020 (to I.A.-D.) and La Ligue Nationale Contre le Cancer (Equipe labellisée 2019 and 2022 to I.P. and I.A.-D.). A.L.C. was supported by Paris University (MENRT grant), J.R.C. by a CRUK Senior Cancer Research Fellowship (RCCSCF-Nov21\100004) and S.E.W.J. by the Swedish Research Council, Torsten Söderberg Foundation and Knut and Alice Wallenberg Foundation. F.G. was supported by grants from the association ‘Chalon sur Saône-Tulipes contre le cancer’ and the Centre de Ressources Biologiques Ferdinand Cabanne. The authors would like to acknowledge the flow cytometry facility at the MRC Weatherall Institute of Molecular Medicine (WIMM), which is supported by the MRC Human Immunology Unit; MRC Molecular Haematology Unit (MC_UU_12009); National Institute for Health Research (NIHR), Oxford Biomedical Research Centre (BRC); Kay Kendall Leukemia Fund (KKL1057), John Fell Fund (131/030 and 101/517), the EPA fund (CF182 and CF170) and by the MRC WIMM Strategic Alliance awards (G0902418 and MC_UU_12025). The authors acknowledge the contributions of N. Ashley at the MRC Weatherall Institute of Molecular Medicine (WIMM) Single Cell Facility and MRC-funded Oxford Consortium for Single-Cell Biology (MR/M00919X/1). The authors would also like to acknowledge the contribution of the WIMM Sequencing Facility, supported by the MRC Human Immunology Unit and by the EPA fund (CF268), the Gustave Roussy flow cytometry platform and mouse facility. We also thank the Oxford Genomics Centre at the Wellcome Centre for Human Genetics (funded by Wellcome Trust grant reference 203141/Z/16/Z) for the generation and initial processing of the OmniExpress SNP array data. The results published here are in whole or part based upon data generated by the TCGA Research Network (https://www.cancer.gov/tcga) and the BeatAML team. The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript."