Tracking rare single donor and recipient immune and leukemia cells after allogeneic hematopoietic cell transplantation using mitochondrial DNA mutations.

Autor:	Penter L; Dana-Farber Cancer Institute, Boston, MA, United States., Cieri N; Dana-Farber Cancer Institute, Boston, MA, United States., Maurer K; Dana-Farber Cancer Institute, Boston, MA, United States., Kwok M; University of Birmingham, Birmingham, United Kingdom., Lyu H; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States., Lu WS; Dana-Farber Cancer Institute, Boston, MA, United States., Oliveira G; Dana-Farber Cancer Institute, Boston, United States., Gohil SH; Broad Institute of MIT and Harvard, Cambridge, MA, United States., Leshchiner I; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, United States., Lareau CA; Memorial Sloan Kettering Cancer Center, New York, NY, United States., Ludwig LS; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Berlin, Germany., Neuberg DS; Dana-Farber Cancer Institute, Boston, MA, United States., Kim HT; Dana-Farber Cancer Institute, Boston, United States., Li S; Dana-Farber Cancer Institute, Boston, MA, United States., Bullinger L; Charité - Universitätsmedizin Berlin, Berlin, Germany., Ritz J; Dana-Farber Cancer Institute, Boston, MA, United States., Getz G; Broad Institute, Cambridge, MA, United States., Garcia JS; Dana-Farber Cancer Institute, Boston, MA, United States., Soiffer RJ; Dana-Farber Cancer Institute, Boston, MA, United States., Livak KJ; Dana-Farber Cancer Institute, Boston, MA, United States., Wu CJ; Dana-Farber Cancer Institute, Boston, MA, United States.
Jazyk:	angličtina
Zdroj:	Blood cancer discovery [Blood Cancer Discov] 2024 Sep 05. Date of Electronic Publication: 2024 Sep 05.
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 co-evolve with somatic nuclear DNA mutations at relapse post-HSCT and provide a sensitive means to monitor these cellular populations. Further, detection of mtDNA mutations via single-cell ATAC with select antigen profiling by sequencing (ASAP-seq) simultaneously determines not only donor and recipient cells, but also their phenotype, at frequencies of 0.1-1%. 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.
Databáze:	MEDLINE
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