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Ruxolitinib treatment reduces monocytic superoxide radical formation without affecting hydrogen peroxide formation or systemic oxidative nucleoside damage in myelofibrosis

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@article{6f6cb228d6df419b9f9ced5e19d1625a,
title = "Ruxolitinib treatment reduces monocytic superoxide radical formation without affecting hydrogen peroxide formation or systemic oxidative nucleoside damage in myelofibrosis",
abstract = "The role of excess reactive oxygen species (ROS) with consequent DNA/RNA damage is now recognized as a hallmark of cancer. In JAK2V617F mutated myeloproliferative neoplasms, ROS have been suggested to be important factors in disease initiation and progression. Ruxolitinib is the most widely used drug for myelofibrosis, because it improves symptom-score. However, both the anti-clonal potential and improvement in overall survival are limited. We investigated the impact of ruxolitinib on formation of superoxide radical and hydrogen peroxide by monocytes in sequentially acquired blood samples from patients with myelofibrosis. We also investigated the impact on RNA and DNA damage by measuring urinary excretion of 8-oxo-Guo and 8-oxo-d-Guo. The formation of superoxide by monocytes was reduced significantly during ruxolitinib therapy, but no impact on the formation of hydrogen peroxide by monocytes or the systemic amount of oxidatively damaged RNA or DNA could be demonstrated. We conclude that ruxolitinib holds little anti-oxidative potential.",
keywords = "DNA damage, hydrogen peroxide, myelofibrosis, Reactive oxygen species, ruxolitinib, superoxide radical",
author = "Bj{\o}rn, {Mads Emil} and Brimnes, {Marie Klinge} and Sif Gudbrandsdottir and Andersen, {Christen Lykkegaard} and Poulsen, {Henrik Enghusen} and Trine Henriksen and Hasselbalch, {Hans Carl} and Nielsen, {Claus Henrik}",
year = "2019",
doi = "10.1080/10428194.2019.1579323",
language = "English",
volume = "60",
pages = "2549--2557",
journal = "Leukemia and Lymphoma",
issn = "1042-8194",
publisher = "Informa Healthcare",
number = "10",

}

RIS

TY - JOUR

T1 - Ruxolitinib treatment reduces monocytic superoxide radical formation without affecting hydrogen peroxide formation or systemic oxidative nucleoside damage in myelofibrosis

AU - Bjørn, Mads Emil

AU - Brimnes, Marie Klinge

AU - Gudbrandsdottir, Sif

AU - Andersen, Christen Lykkegaard

AU - Poulsen, Henrik Enghusen

AU - Henriksen, Trine

AU - Hasselbalch, Hans Carl

AU - Nielsen, Claus Henrik

PY - 2019

Y1 - 2019

N2 - The role of excess reactive oxygen species (ROS) with consequent DNA/RNA damage is now recognized as a hallmark of cancer. In JAK2V617F mutated myeloproliferative neoplasms, ROS have been suggested to be important factors in disease initiation and progression. Ruxolitinib is the most widely used drug for myelofibrosis, because it improves symptom-score. However, both the anti-clonal potential and improvement in overall survival are limited. We investigated the impact of ruxolitinib on formation of superoxide radical and hydrogen peroxide by monocytes in sequentially acquired blood samples from patients with myelofibrosis. We also investigated the impact on RNA and DNA damage by measuring urinary excretion of 8-oxo-Guo and 8-oxo-d-Guo. The formation of superoxide by monocytes was reduced significantly during ruxolitinib therapy, but no impact on the formation of hydrogen peroxide by monocytes or the systemic amount of oxidatively damaged RNA or DNA could be demonstrated. We conclude that ruxolitinib holds little anti-oxidative potential.

AB - The role of excess reactive oxygen species (ROS) with consequent DNA/RNA damage is now recognized as a hallmark of cancer. In JAK2V617F mutated myeloproliferative neoplasms, ROS have been suggested to be important factors in disease initiation and progression. Ruxolitinib is the most widely used drug for myelofibrosis, because it improves symptom-score. However, both the anti-clonal potential and improvement in overall survival are limited. We investigated the impact of ruxolitinib on formation of superoxide radical and hydrogen peroxide by monocytes in sequentially acquired blood samples from patients with myelofibrosis. We also investigated the impact on RNA and DNA damage by measuring urinary excretion of 8-oxo-Guo and 8-oxo-d-Guo. The formation of superoxide by monocytes was reduced significantly during ruxolitinib therapy, but no impact on the formation of hydrogen peroxide by monocytes or the systemic amount of oxidatively damaged RNA or DNA could be demonstrated. We conclude that ruxolitinib holds little anti-oxidative potential.

KW - DNA damage

KW - hydrogen peroxide

KW - myelofibrosis

KW - Reactive oxygen species

KW - ruxolitinib

KW - superoxide radical

U2 - 10.1080/10428194.2019.1579323

DO - 10.1080/10428194.2019.1579323

M3 - Journal article

VL - 60

SP - 2549

EP - 2557

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

SN - 1042-8194

IS - 10

ER -

ID: 56643066