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

Abstract 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 thrombocythemia 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.