Expression of myeloperoxidase enhances the chemosensitivity of leukemia cells through the generation of reactive oxygen species and the nitration of protein.
Myeloperoxidase (MPO), a pivotal lineage marker for acute myeloid leukemia (AML), has been also shown to have a prognostic value: a high percentage of MPO-positive blasts correlates to favorable prognosis. To understand the relationship between the expression of MPO in leukemia cells and the response to chemotherapeutic agents, we established MPO-expressing K562 leukemia cell lines and then treated them with cytosine arabinocide (AraC). Cells expressing wild-type MPO, but not mutant MPO that could not mature, died earlier of apoptosis than control K562 cells. Reactive oxygen species (ROS) were generated more in leukemia cells expressing MPO, and the generation was abrogated by MPO inhibitors or antioxidants. Tyrosine nitration of cellular protein also increased more in MPO-expressing K562 cells than control cells after treatment with AraC. In clinical samples, CD34-positive AML cells from high-MPO cases showed a tendency to be sensitive to AraC in the colony-formation assay, and the generation of ROS and the nitration of protein were observed only when the percentage of MPO-expressing cells was high. These data suggest that MPO enhances the chemosensitivity of AML through the generation of ROS and the nitration of proteins.
Sawayama
Y
Y
Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Miyazaki
Y
Y
Ando
K
K
Horio
K
K
Tsutsumi
C
C
Imanishi
D
D
Tsushima
H
H
Imaizumi
Y
Y
Hata
T
T
Fukushima
T
T
Yoshida
S
S
Onimaru
Y
Y
Iwanaga
M
M
Taguchi
J
J
Kuriyama
K
K
Tomonaga
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D015538:Nitrosation; D009195:Peroxidase / Q000032:analysis / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D009195:Peroxidase