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| Item Type: | Article |
|---|---|
| Title: | Dynamics of clonal hematopoiesis and cellular responses to stress-induced toxicity in autologous stem cell transplantation |
| Creators Name: | Stein, Catarina M., Hablesreiter, Raphael, Christen, Friederike, Löwe, Pelle, Fustero-Torre, Coral, Kopp, Klara, Locher, Benjamin N., Nitsch, Lena, Altwasser, Robert, Kerschbaum, Johanna Franziska, Bullinger, Lars, Ludwig, Leif S., Strzelecka, Paulina M. and Damm, Frederik |
| Abstract: | Autologous stem cell transplantation (ASCT) involves harvesting hematopoietic stem and progenitor cells (HSPCs) prior to chemotherapy and subsequent repopulation of the bone marrow. This process imposes a bottleneck, providing a framework to dissect the unresolved short- and long-term clonal dynamics during hematopoietic reconstitution. By integrating bulk error-corrected targeted sequencing of clonal hematopoiesis (CH)-associated genes with mitochondrial single-cell Assay for Transposase-Accessible Chromatin sequencing (mtscATAC-seq), we characterized mutational trajectories in frequently altered hematological genes and traced clonal evolution through somatic mitochondrial DNA variants, revealing post-transplant cellular heterogeneity and clonal architecture. Among 60 patients (multiple myeloma, n = 51; non-Hodgkin lymphoma, n = 6; Hodgkin lymphoma, n = 3), CH-associated mutations were identified in 53% pre-ASCT, predominantly involving DNMT3A. A transient increase in mutation counts and gene diversity occurred 10-25 days post-ASCT, with a gradual clonal expansion two years post-transplantation. Tandem ASCT amplified clonal complexity, with a twofold increase in mutation count and gene-level diversity, while preserving clonal trajectories across both transplant courses. Mitochondrial single-cell profiling in longitudinal samples of 3 patients showed patient-specific immune reconstitution and clonal dynamics, with balanced multilineage output from graft HSPCs. Collectively, our findings provide a firsthand comprehensive view of ASCT-induced clonal dynamics and immune reconstitution, paving the way for targeted gene-specific post-transplant monitoring. |
| Source: | Leukemia |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date: | 19 December 2025 |
| Official Publication: | https://doi.org/10.1038/s41375-025-02823-z |
| PubMed: | View item in PubMed |
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