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

TY - JOUR

T1 - B-cell frequencies and immunoregulatory phenotypes in myeloproliferative neoplasms: Influence of ruxolitinib, interferon-α2, or combination treatment

AU - Sørensen, Anders Lindholm

AU - Bjørn, Mads Emil

AU - Riley, Caroline H

AU - Holmstrøm, M

AU - Andersen, Mads Hald

AU - Svane, Inge Marie

AU - Mikkelsen, Stine Ulrik

AU - Skov, Vibe

AU - Kjaer, Lasse

AU - Hasselbalch, Hans Carl

AU - Nielsen, Claus Henrik

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

U2 - 10.1111/ejh.13292

DO - 10.1111/ejh.13292

M3 - Journal article

C2 - 31297883

SN - 0902-4441

SP - 351

EP - 361

JO - European Journal of Haematology

JF - European Journal of Haematology

ER -