Tracking Rare Single Donor and Recipient Immune and Leukemia Cells after Allogeneic Hematopoietic Cell Transplantation Using Mitochondrial DNA Mutations.

Autor:	Penter L; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Department of Hematology, Oncology, and Tumorimmunology, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; Berlin Institute of Health at Charité-Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Digital Clinician Scientist Program, Berlin, Germany., Cieri N; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Maurer K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Kwok M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom., Lyu H; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, Massachusetts., Lu WS; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, Massachusetts., Oliveira G; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Gohil SH; Department of Haematology, University College London Hospitals, London, United Kingdom., Leshchiner I; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts., Lareau CA; Memorial Sloan Kettering Cancer Center, New York City, New York., Ludwig LS; Department of Hematology, Oncology, and Tumorimmunology, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; Berlin Institute of Health at Charité Universitätsmedizin Berlin, Berlin, Germany.; Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin Institute for Medical Systems Biology, Berlin, Germany., Neuberg DS; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts., Kim HT; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts., Li S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, Massachusetts., Bullinger L; Department of Hematology, Oncology, and Tumorimmunology, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Ritz J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Getz G; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Garcia JS; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Soiffer RJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Livak KJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, Massachusetts., Wu CJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.; Harvard Medical School, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	Blood cancer discovery [Blood Cancer Discov] 2024 Nov 01; Vol. 5 (6), pp. 442-459.
DOI:	10.1158/2643-3230.BCD-23-0138
Abstrakt:	Combined tracking of clonal evolution and chimeric cell phenotypes could enable detection of the key cellular populations associated with response following therapy, including after allogeneic hematopoietic stem cell transplantation (HSCT). We demonstrate that mitochondrial DNA (mtDNA) mutations coevolve with somatic nuclear DNA mutations at relapse post-HSCT and provide a sensitive means to monitor these cellular populations. Furthermore, detection of mtDNA mutations via single-cell assay for transposase-accessible chromatin with select antigen profiling by sequencing (ASAP-seq) simultaneously determines not only donor and recipient cells but also their phenotype at frequencies of 0.1% to 1%. Finally, integration of mtDNA mutations, surface markers, and chromatin accessibility profiles enables the phenotypic resolution of leukemic populations from normal immune cells, thereby providing fresh insights into residual donor-derived engraftment and short-term clonal evolution following therapy for post-transplant leukemia relapse. As throughput evolves, we envision future development of single-cell sequencing-based post-transplant monitoring as a powerful approach for guiding clinical decision-making. Significance: mtDNA mutations enable single-cell tracking of leukemic clonal evolution and donor-recipient origin following allogeneic HSCT. This provides unprecedented insight into chimeric cellular phenotypes of early immune reconstitution, incipient relapse, and quality of donor engraftment with immediate translational potential for future clinical post-transplant monitoring and decision-making. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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