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Journal Articles Nature Communications Year : 2023

Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation

Hetty E Carraway
Ronald Sobecks
  • Function : Author
Betty K Hamilton
Valeria Visconte
Jaroslaw P Maciejewski

Abstract

Abstract 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.
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Dates and versions

hal-04162108 , version 1 (14-07-2023)

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Simona Pagliuca, Carmelo Gurnari, Colin Hercus, Sébastien Hergalant, Sanghee Hong, et al.. Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation. Nature Communications, 2023, 14 (1), pp.3153. ⟨10.1038/s41467-023-38113-4⟩. ⟨hal-04162108⟩
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