Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation

Simona Pagliuca, Carmelo Gurnari, Colin Hercus, Sébastien Hergalant, Sanghee Hong, Adele Dhuyser, Maud D’Aveni, Alice Aarnink, Marie Thérèse Rubio, Pierre Feugier, Francesca Ferraro, Hetty E. Carraway, Ronald Sobecks, Betty K. Hamilton, Navneet S. Majhail, Valeria Visconte and Jaroslaw P. Maciejewski ()
Additional contact information
Simona Pagliuca: Taussig Cancer Institute, Cleveland Clinic
Carmelo Gurnari: Taussig Cancer Institute, Cleveland Clinic
Colin Hercus: Novocraft Technologies Sdn Bhd
Sébastien Hergalant: University of Lorraine
Sanghee Hong: Duke University School of Medicine
Adele Dhuyser: CNRS UMR 7365, IMoPA, Biopole of University of Lorraine
Maud D’Aveni: CHRU de Nancy
Alice Aarnink: CNRS UMR 7365, IMoPA, Biopole of University of Lorraine
Marie Thérèse Rubio: CHRU de Nancy
Pierre Feugier: CHRU de Nancy
Francesca Ferraro: Washington University School of Medicine in St. Louis
Hetty E. Carraway: Taussig Cancer Institute, Cleveland Clinic
Ronald Sobecks: Taussig Cancer Institute, Cleveland Clinic
Betty K. Hamilton: Taussig Cancer Institute, Cleveland Clinic
Navneet S. Majhail: Sarah Cannon Transplant and Cellular Therapy Network
Valeria Visconte: Taussig Cancer Institute, Cleveland Clinic
Jaroslaw P. Maciejewski: Taussig Cancer Institute, Cleveland Clinic

Nature Communications, 2023, vol. 14, issue 1, 1-12

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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-38113-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38113-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-38113-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().