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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: |
Stein, Catarina M.  ORCID: https://orcid.org/0000-0002-9015-7671, Hablesreiter, Raphael ORCID: https://orcid.org/0000-0002-4586-932X, Christen, Friederike ORCID: https://orcid.org/0000-0001-8868-2533, Löwe, Pelle, Fustero-Torre, Coral, Kopp, Klara, Locher, Benjamin N., Nitsch, Lena ORCID: https://orcid.org/0000-0003-0775-1969, Altwasser, Robert ORCID: https://orcid.org/0009-0002-6216-6068, Kerschbaum, Johanna Franziska, Bullinger, Lars ORCID: https://orcid.org/0000-0002-5890-5510, Ludwig, Leif S. ORCID: https://orcid.org/0000-0002-2916-2164, Strzelecka, Paulina M. ORCID: https://orcid.org/0000-0003-0226-6788 and Damm, Frederik ORCID: https://orcid.org/0000-0001-5553-1173
|
| 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. |
| Keywords: | Autologous Transplantation, Clonal Evolution, Clonal Hematopoiesis, DNA Methyltransferase 3A, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Hodgkin Disease, Mitochondrial DNA, Multiple Myeloma, Mutation, Non-Hodgkin Lymphoma, Physiological Stress |
| Source: | Leukemia |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Volume: | 40 |
| Number: | 2 |
| Page Range: | 314-324 |
| Date: | February 2026 |
| Official Publication: | https://doi.org/10.1038/s41375-025-02823-z |
| PubMed: | View item in PubMed |
| Related to: |
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