B-cell frequencies and immunoregulatory phenotypes in myeloproliferative neoplasms: influence of ruxolitinib, interferon-α2, or combination treatment

OBJECTIVE: Given a proposed role for PD-L1+ and IL-10-producing B-cell subsets in promoting certain cancers, we sought to characterize the frequency and phenotype of B cells in patients with chronic myeloproliferative neoplasms (MPNs) and the influence of ruxolitinib and interferon-α2 therapy.

METHODS: We analyzed B-cell frequencies and phenotype in patients with MPNs (n=107), before and during treatment with ruxolitinib (n=29), interferon-α2 (n=21), or the two drugs in combination (COMBI) (n=42) and healthy donors (HDs) (n=52) using flow cytometry.

RESULTS: Myelofibrosis patients had lower lymphocyte counts and proportions of B cells than patients with essential thrombocytosis or polycythemia vera and HDs. The B-cell count correlated inversely with JAK2-V617F allele burden and spleen size and increased after ruxolitinib or COMBI treatment. The proportions of PD-L1+ B cells and PD-1+ B cells were significantly higher in patients with myelofibrosis or polycythemia vera than in HDs and decreased during ruxolitinib and COMBI treatment. The proportions of TNF-α+ and IL-6+ B cells were elevated in myelofibrosis patients. The proportion of IL-6+ B cells decreased, and the proportion of IL-10+ B cells increased during ruxolitinib treatment.

CONCLUSION: B-cell frequency and phenotype were altered in MPN patients. Ruxolitinib therapy had marked effects on both frequency and phenotype. This article is protected by copyright. All rights reserved.