PD-L1 overexpression correlates with JAK2-V617F mutational burden and is associated with 9p uniparental disomy in myeloproliferative neoplasms.

ABSTRACT: Myeloproliferative neoplasms (MPN) are chronic stem cell disorders characterized by enhanced proliferation of myeloid cells, immune deregulation, and drug resistance. JAK2 somatic mutations drive the disease in 50-60% and CALR mutations in 25-30% of cases. Published data suggest that JAK2-V617F-mutated MPN cells express the resistance-related checkpoint PD-L1. By applying RNA-sequencing on granulocytes of 113 MPN patients, we demonstrate that PD-L1 expression is highest among polycythemia vera patients and that PD-L1 expression correlates with JAK2-V617F mutational burden (R = 0.52; p < .0001). Single nucleotide polymorphism (SNP) arrays showed that chromosome 9p uniparental disomy (UPD) covers both PD-L1 and JAK2 in all MPN patients examined. MPN cells in JAK2-V617F-positive patients expr

SUBMITTER: Milosevic Feenstra JD 

PROVIDER: S-EPMC9306481 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature