Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation.
Journal
Research square
Titre abrégé: Res Sq
Pays: United States
ID NLM: 101768035
Informations de publication
Date de publication:
05 Apr 2023
05 Apr 2023
Historique:
medline:
18
4
2023
entrez:
17
4
2023
pubmed:
18
4
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 experience 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 reactions and response to immunomodulatory strategies. These findings define key molecular modes of post-transplant leukemia escape contributing to relapse.
Identifiants
pubmed: 37066269
doi: 10.21203/rs.3.rs-2773498/v1
pmc: PMC10104200
pii:
doi:
Types de publication
Preprint
Langues
eng
Commentaires et corrections
Type : UpdateIn
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