The <i>JAK2</i> 46/1 haplotype influences PD-L1 expression

Although described more than a decade ago, the mechanism by which the JAK2 46/1 haplotype increases the risk of developing JAK2-mutated myeloproliferative neoplasms (MPNs) remains unexplained. Inflammation and immunity are linked to MPN development and thus could be relevant to the mechanism by which 46/1 mediates its effect. Here, we show that programmed death-1 receptor ligand (PD-L1) expression is elevated in 46/1 haplotype, both in healthy carriers and in CD34+ cells from patients with MPN. Using circular chromosome conformation capture, we observed that PD-L1 and the neighboring PD-L2 loci physically interact with JAK2 in a manner that differs between 46/1 and nonrisk haplotypes. CRISPR/Cas9 genome editing identified a region within JAK2 intron 2 that influences both JAK2 and PD-L1 expression. We suggest that increased PD-L1 expression may be relevant to the mechanism by which 46/1 leads to an increased inherited risk of developing MPN.

Authors

Institutions

Publication Details

Journal
Blood
Published
2025-02-07
DOI
https://doi.org/10.1182/blood.2023023787
Citations
2
Primary Topic
Myeloproliferative Neoplasms: Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
3.25

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

The JAK2 46/1 haplotype influences PD-L1 expression

Andrew Chase, William Tapper, Miguel Manzanares, Joaquín Martínez‐López et al.
2 citations
Blood
Myeloproliferative Neoplasms: Diagnosis and Treatment
3.25
article

The JAK2 46/1 haplotype influences PD-L1 expression

Andrew Chase, William Tapper, Miguel Manzanares, Joaquín Martínez‐López, Nicholas C.P. Cross, María Tiana, Raquel Rouco, Jesús Victorino, Gonzalo Carreño‐Tarragona, Alejandra Leivas, Rosa María Ayala, Roberto García-Vicente, Andrea Maidana
article en
2 citations

Abstract

Although described more than a decade ago, the mechanism by which the JAK2 46/1 haplotype increases the risk of developing JAK2-mutated myeloproliferative neoplasms (MPNs) remains unexplained. Inflammation and immunity are linked to MPN development and thus could be relevant to the mechanism by which 46/1 mediates its effect. Here, we show that programmed death-1 receptor ligand (PD-L1) expression is elevated in 46/1 haplotype, both in healthy carriers and in CD34+ cells from patients with MPN. Using circular chromosome conformation capture, we observed that PD-L1 and the neighboring PD-L2 loci physically interact with JAK2 in a manner that differs between 46/1 and nonrisk haplotypes. CRISPR/Cas9 genome editing identified a region within JAK2 intron 2 that influences both JAK2 and PD-L1 expression. We suggest that increased PD-L1 expression may be relevant to the mechanism by which 46/1 leads to an increased inherited risk of developing MPN.

BloodVol. 145(19)
Universidad Francisco de Vitoria (ES), Instituto de Salud Carlos III (ES), Spanish National Centre for Cardiovascular Research (ES), Research Institute Hospital 12 de Octubre (ES), Spanish National Cancer Research Centre (ES), Hospital Universitario 12 De Octubre (ES), Centro de Investigación Biomédica en Red (ES), Centro de Biología Molecular Severo Ochoa (ES), Centro de Investigación Biomédica en Red de Cáncer (ES), University of Southampton (GB), Universidad Autónoma de Madrid (ES)
Fundación Ramón Areces, Instituto de Salud Carlos III, Agencia Estatal de Investigación
Openalex Percentile: Top 10%
Myeloproliferative Neoplasms: Diagnosis and Treatment
3.25
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.