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

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@article{144fcbaa63b94c96add05ab018e407c3,
title = "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 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.",
author = "S{\o}rensen, {A L} and Bj{\o}rn, {M E} and Riley, {C H} and M Holmstr{\o}m and Andersen, {M H} and Svane, {I M} and Mikkelsen, {S U} and V Skov and L Kjaer and Hasselbalch, {H C} and Nielsen, {C H}",
note = "{\circledC} 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
year = "2019",
month = "10",
doi = "10.1111/ejh.13292",
language = "English",
volume = "103",
pages = "351--361",
journal = "European Journal of Haematology",
issn = "0902-4441",
publisher = "Wiley-Blackwell Munksgaard",
number = "4",

}

RIS

TY - JOUR

T1 - B-cell frequencies and immunoregulatory phenotypes in myeloproliferative neoplasms

T2 - influence of ruxolitinib, interferon-α2, or combination treatment

AU - Sørensen, A L

AU - Bjørn, M E

AU - Riley, C H

AU - Holmstrøm, M

AU - Andersen, M H

AU - Svane, I M

AU - Mikkelsen, S U

AU - Skov, V

AU - Kjaer, L

AU - Hasselbalch, H C

AU - Nielsen, C H

N1 - © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2019/10

Y1 - 2019/10

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 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.

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 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.

UR - http://www.scopus.com/inward/record.url?scp=85070823889&partnerID=8YFLogxK

U2 - 10.1111/ejh.13292

DO - 10.1111/ejh.13292

M3 - Journal article

VL - 103

SP - 351

EP - 361

JO - European Journal of Haematology

JF - European Journal of Haematology

SN - 0902-4441

IS - 4

ER -

ID: 57728420