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Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation.

Publication ,  Journal Article
Pagliuca, S; Gurnari, C; Hercus, C; Hergalant, S; Hong, S; Dhuyser, A; D'Aveni, M; Aarnink, A; Rubio, MT; Feugier, P; Ferraro, F; Carraway, HE ...
Published in: Res Sq
April 5, 2023

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.

Duke Scholars

Published In

Res Sq

DOI

Publication Date

April 5, 2023

Location

United States
 

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Pagliuca, S., Gurnari, C., Hercus, C., Hergalant, S., Hong, S., Dhuyser, A., … Maciejewski, J. P. (2023). Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation. Res Sq. https://doi.org/10.21203/rs.3.rs-2773498/v1
Pagliuca, Simona, Carmelo Gurnari, Colin Hercus, Sébastien Hergalant, Sanghee Hong, Adele Dhuyser, Maud D’Aveni, et al. “Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation.Res Sq, April 5, 2023. https://doi.org/10.21203/rs.3.rs-2773498/v1.
Pagliuca S, Gurnari C, Hercus C, Hergalant S, Hong S, Dhuyser A, et al. Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation. Res Sq. 2023 Apr 5;
Pagliuca, Simona, et al. “Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation.Res Sq, Apr. 2023. Pubmed, doi:10.21203/rs.3.rs-2773498/v1.
Pagliuca S, Gurnari C, Hercus C, Hergalant S, Hong S, Dhuyser A, D’Aveni M, Aarnink A, Rubio MT, Feugier P, Ferraro F, Carraway HE, Sobecks R, Hamilton BK, Majhail NS, Visconte V, Maciejewski JP. Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation. Res Sq. 2023 Apr 5;

Published In

Res Sq

DOI

Publication Date

April 5, 2023

Location

United States