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@ARTICLE{Stein:307371,
author = {C. M. Stein and R. Hablesreiter and F. Christen and P.
Löwe and C. Fustero-Torre and K. Kopp and B. N. Locher and
L. Nitsch and R. Altwasser and J. F. Kerschbaum and L.
Bullinger$^*$ and L. S. Ludwig and P. M. Strzelecka and F.
Damm$^*$},
title = {{D}ynamics of clonal hematopoiesis and cellular responses
to stress-induced toxicity in autologous stem cell
transplantation.},
journal = {Leukemia},
volume = {nn},
issn = {0887-6924},
address = {London},
publisher = {Springer Nature},
reportid = {DKFZ-2025-03015},
pages = {nn},
year = {2025},
note = {epub},
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.},
cin = {BE01},
ddc = {610},
cid = {I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41419602},
doi = {10.1038/s41375-025-02823-z},
url = {https://inrepo02.dkfz.de/record/307371},
}