The role of clonal hematopoiesis as driver of therapy-related myeloid neoplasms after autologous stem cell transplantation.
Clonal Hematopoiesis
/ genetics
Core Binding Factor Alpha 2 Subunit
/ genetics
Hematopoiesis
/ genetics
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
Mutation
Myeloproliferative Disorders
/ complications
Neoplasms, Second Primary
/ genetics
Transplantation, Autologous
/ adverse effects
Autologous stem cell transplantation
Clonal hematopoiesis
Next-generation sequencing
Therapy-related myeloid neoplasms
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
29
10
2021
accepted:
22
02
2022
pubmed:
6
4
2022
medline:
10
5
2022
entrez:
5
4
2022
Statut:
ppublish
Résumé
Therapy-related myeloid neoplasm (t-MN) is a threatening complication of autologous stem cell transplantation (ASCT). Detecting clonal hematopoiesis (CH) mutations in cryopreserved cells before ASCT has been associated with a higher risk of t-MN, but the evolution of molecular abnormalities from pre-ASCT to t-MN, within the same patient, remains to be elucidated. We evaluated the mutational profile of 19 lymphoma/myeloma patients, at both pre-ASCT and t-MN diagnosis, using a targeted NGS approach; 26 non-developing t-MN control patients were also studied pre-ASCT. At ASCT, we found a higher frequency of CH in patients developing t-MN (58%) than in those who did not (23%) (P = 0.029); mutations in epigenetic (DNMT3A, TET2, and ASXL1) and DNA repair genes (PPM1D, RAD21, TP53, and STAG2) were the most represented. At t-MN, CH increased to 82% of patients. Cumulative mutational burden and variant allele frequency (VAF) also increased at t-MN. CH clones detected at ASCT were found at t-MN in eight out of 16 patients, mainly with stable VAF. Among the new driver mutations appeared at t-MN, TP53 increased from one to 13 mutations, in nine patients; being associated with complex karyotype. Mutations in transcription factor (RUNX1, CEBPA) and intracellular signaling genes (FLT3, RAS genes) also increased from three to 17 mutations in eight patients, presenting with a normal karyotype. Overall, we found that preexisting CH at ASCT rarely causes t-MN directly, but may rather facilitate the appearance of new mutations, especially those involving TP53, RUNX1, and RAS, that can drive the evolution to t-MN of at least two distinct types.
Identifiants
pubmed: 35380239
doi: 10.1007/s00277-022-04806-x
pii: 10.1007/s00277-022-04806-x
doi:
Substances chimiques
Core Binding Factor Alpha 2 Subunit
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1227-1237Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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