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| Item Type: | Article |
|---|---|
| Title: | Tracking rare single donor and recipient immune and leukemia cells after allogeneic hematopoietic cell transplantation using mitochondrial DNA mutations |
| Creators Name: | Penter, L., Cieri, N., Maurer, K., Kwok, M., Lyu, H., Lu, W.S., Oliveira, G., Gohil, S.H., Leshchiner, I., Lareau, C.A., Ludwig, L.S., Neuberg, D.S., Kim, H.T., Li, S., Bullinger, L., Ritz, J., Getz, G., Garcia, J.S., Soiffer, R.J., Livak, K.J. and Wu, C.J. |
| Abstract: | 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. |
| Keywords: | Mitochondrial DNA Mutations, Measurable Residual Disease, Allogeneic Hematopoietic Stem, Cell Transplantation, Microchimerism, Clonal Evolution, Single Cell Proteogenomics |
| Source: | Blood Cancer Discovery |
| ISSN: | 2643-3230 |
| Publisher: | American Association for Cancer Research |
| Volume: | 5 |
| Number: | 6 |
| Page Range: | 442-459 |
| Date: | 1 November 2024 |
| Official Publication: | https://doi.org/10.1158/2643-3230.BCD-23-0138 |
| PubMed: | View item in PubMed |
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