Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
31 05 2023
31 05 2023
Historique:
received:
09
10
2022
accepted:
13
04
2023
medline:
2
6
2023
pubmed:
1
6
2023
entrez:
31
5
2023
Statut:
epublish
Résumé
Graft-versus-leukemia (GvL) reactions are responsible for the effectiveness of allogeneic hematopoietic cell transplantation as a treatment modality for myeloid neoplasia, whereby donor T- effector cells recognize leukemia neoantigens. However, a substantial fraction of patients experiences relapses because of the failure of the immunological responses to control leukemic outgrowth. Here, through a broad immunogenetic study, we demonstrate that germline and somatic reduction of human leucocyte antigen (HLA) heterogeneity enhances the risk of leukemic recurrence. We show that preexistent germline-encoded low evolutionary divergence of class II HLA genotypes constitutes an independent factor associated with disease relapse and that acquisition of clonal somatic defects in HLA alleles may lead to escape from GvL control. Both class I and II HLA genes are targeted by somatic mutations as clonal selection factors potentially impairing cellular immune responses and response to immunomodulatory strategies. These findings define key molecular modes of post-transplant leukemia escape contributing to relapse.
Identifiants
pubmed: 37258544
doi: 10.1038/s41467-023-38113-4
pii: 10.1038/s41467-023-38113-4
pmc: PMC10232425
doi:
Substances chimiques
HLA Antigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3153Subventions
Organisme : NHLBI NIH HHS
ID : R35 HL135795
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL123904
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128425
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL132071
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023. The Author(s).
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