The relevance of HLA class II genes in JAK2 V617F-positive myeloproliferative neoplasms.
Hum Immunol
; 84(3): 199-207, 2023 Mar.
Article
em En
| MEDLINE
| ID: mdl-36707384
ABSTRACT
In the present study we analyzed the relevance of HLA class II in JAK2 V617F-positive (JAK2 V617F+) myeloproliferative neoplasms (MPNs) focusing on genotype diversity, associations with specific alleles and haplotypes and the level of gene expression. One hundred and thirty-nine JAK2 V617F+ MPN patients and 1083 healthy controls, typed by Next generation sequencing (NGS) were included in the study. Multivariate generalized linear models with age as a covariate were applied for analysis of HLA-II allele and haplotype associations. Publicly available gene expression datasets were used to analyze HLA-II pathway genes expression in CD34+ stem cells (SCs) from MPN patients and healthy controls. We did not observe differences in HLA evolutionary divergence (HED) between JAK2 V617F+ MPNs and healthy controls. Two alleles HLA-DPB1*0301, DQB1*0402 and 4 haplotypes DPB1*0201-DQA1*0505-DQB1*0301-DRB1*1101, DPB1*0402-DQA1*0505-DQB1*0301-DRB1*1103, DPB1*0201-DQA1*0104-DQB1*0503-DRB1*1404, and DPB1*0401-DQA1*0301-DQB1*0302-DRB1*0401 had significantly lower frequency in MPN patients compared to controls. Additionally, we observed HLA-II alleles and haplotypes with statistically higher frequencies in JAK2 V617F+ patients. Differential gene expression analysis showed down-regulation of HLA-DRB1, -DRA, -DMA, -DMB, -DOA,-DRB4, CIITA, and CD74 genes in JAK2 V617F+ MPN CD34+ SCs as compared to normal CD34 + SCs. In conclusion, this study provides evidence for the pleiotropic effects of HLA-II genes in JAK2 V617F-driven MPNs.
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Base de dados:
MEDLINE
Assunto principal:
Genes MHC da Classe II
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Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article