TY  - JOUR
A1  - Ortmann, Christina Ann
A1  - Dorsheimer, Lena
A1  - Abou-El-Ardat, Khalil
A1  - Hoffrichter, Jennifer
A1  - Aßmus, Birgit
A1  - Bönig, Halvard-Björn
A1  - Scholz, Anica
A1  - Pfeifer, Heike
A1  - Martin, Hans
A1  - Schmid, Tobias
A1  - Brüne, Bernhard
A1  - Scheich, Sebastian
A1  - Steffen, Björn
A1  - Riemann, Julia
A1  - Hermann, Stella
A1  - Dukat, Alexandra
A1  - Bug, Gesine
A1  - Brandts, Christian Hubertus
A1  - Wagner, Sebastian Alexander
A1  - Serve, Hubert
A1  - Rieger, Michael A.
T1  - Functional dominance of CHIP-mutated hematopoietic stem cells in patients undergoing autologous transplantation
T2  - Cell reports
N2  - Clonal hematopoiesis of indeterminate potential (CHIP) is caused by recurrent somatic mutations leading to clonal blood cell expansion. However, direct evidence of the fitness of CHIP-mutated human hematopoietic stem cells (HSCs) in blood reconstitution is lacking. Because myeloablative treatment and transplantation enforce stress on HSCs, we followed 81 patients with solid tumors or lymphoid diseases undergoing autologous stem cell transplantation (ASCT) for the development of CHIP. We found a high incidence of CHIP (22%) after ASCT with a high mean variant allele frequency (VAF) of 10.7%. Most mutations were already present in the graft, albeit at lower VAFs, demonstrating a selective reconstitution advantage of mutated HSCs after ASCT. However, patients with CHIP mutations in DNA-damage response genes showed delayed neutrophil reconstitution. Thus, CHIP-mutated stem and progenitor cells largely gain on clone size upon ASCT-related blood reconstitution, leading to an increased future risk of CHIP-associated complications.
KW  - ASCT
KW  - CHIP
KW  - autologous stem cell transplantation
KW  - chemotherapy
KW  - clonal dominance
KW  - clonal hematopoiesis
KW  - hematopoietic stem cells
KW  - hematopoietic stress
KW  - leukemia
KW  - somatic mutations
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50331
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-503316
SN  - 2211-1247
N1  - This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
VL  - 27
IS  - 7
SP  - 2022
EP  - 2028.e3
PB  - Cell Press ; Elsevier
CY  - Maryland Heights, MO ; [New York, NY]
ER  -