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
C2 - 30785365
SN - 1042-8194
VL - 60
SP - 2549
EP - 2557
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 10
ER -