Journal Article Epublish 2 citations
PubMed: 41246448 DOI: 10.1002/hem3.70261
HLA diversity is associated with TKI response and treatment-free remission in chronic myeloid leukemia.
Hemasphere 9(11):e70261
Authors: Charles Toulemonde, Valérie Dubois, Christophe Bouvier, Alexandre Ridao, Marie-Claire Archier, Marie Balsat, Sophie Ducastelle, Fiorenza Barraco, Gaelle Fossard, Julie Hildt, Julien Bollard, Mauricette Michallet, Hélène Labussière-Wallet, Sandrine Hayette, Franck-Emmanuel Nicolini, Vincent Alcazer
Affiliations
- Service d'Hématologie clinique, Centre Hospitalier Lyon Sud Hospices Civils de Lyon Pierre Bénite France.
- Laboratoire HLA Etablissement Français du Sang Décines France.
- Service d'Hématologie clinique & INSERM U1052, CRCL Centre Léon Bérard Lyon France.
- Laboratoire d'Hématologie, Centre Hospitalier Lyon Sud Hospices Civils de Lyon Pierre-Bénite France.
- Centre International de Recherche en Infectiologie, INSERM U1111 CNRS UMR530 Université Lyon 1 Lyon France.
Abstract
Immune surveillance is increasingly recognized as a key determinant of cancer treatment outcomes. However, the impact of Human Leukocyte Antigen (HLA) diversity in chronic myeloid leukemia (CML) remains poorly understood and has been scarcely investigated. We retrospectively analyzed 367 CML patients with high-resolution HLA typing to investigate the impact of HLA allele distribution and HLA evolutionary divergence (HED) on disease susceptibility, molecular response, and treatment-free remission (TFR). Compared to 2832 healthy donors, CML patients exhibited significantly lower HED scores for all class I loci (A, B, C) and HLA-DQB1 (FDR < 0.001), suggesting a narrower immunopeptidome repertoire at diagnosis. Specific alleles, such as HLA-A*30:01 (OR [95% CI] = 2.08 [1.26-3.25]) and B*14:02 (OR = 1.90 [1.26-2.79]), were associated with increased CML risk (FDR < 0.01). Among 289 patients with clinical follow-up, HLA-DQB1*06:04 (aHR [95% CI] = 3.71 [1.57-8.77]) and DRB1*13:02 (aHR = 3.95 [1.77-8.81]) were associated with faster MR4 achievement in imatinib-treated patients (FDR < 0.01), while B*44:02 (aHR = 4.83 [1.62-14.41]) predicted favorable response to dasatinib (FDR < 0.05). In the TFR cohort (n = 105), alleles A*26:01 (aHR = 3.47 [1.44-8.38]), A32:01 (aHR = 3.28 [1.52-7.09], FDR < 0.05), and B18:01 (aHR = 12.96 [3.59-46.77], FDR < 0.001) were significantly associated with increased relapse risk. Conversely, a higher HED score for HLA-C was associated with improved TFR in dasatinib-treated patients (P = 0.0067). These findings suggest that HLA genotype and class-specific HED may influence CML susceptibility and outcomes and could inform TKI selection and discontinuation strategies.
MeSH
Dasatinib, Leukemia, Leukemia, Myeloid, Alleles, Therapeutics, Leukemia, Myelogenous, Chronic, Bcr-Abl Positive