TY - JOUR
AB - Diffuse large B‑cell lymphoma (DLBCL) is a clinically heterogeneous lymphoid malignancy that is the most common type of lymphoma in Japan. Previous studies have demonstrated that patients with DLBCL have a poor prognosis due to increased levels of indoleamine 2,3‑dioxygnase and kynurenine (KYN). However, the roles of metabolites acting downstream of KYN and associated enzymes are not fully understood. The present study investigated the role of kynurenine 3‑monooxygenase (KMO), which catalyzes the conversion of KYN to 3‑hydroxykynurenine (3‑HK), using serum samples from patients with DLBCL and human DLBCL cell lines with different KMO expression [STR‑428 cells with high levels of KMO expression (KMOhigh) and KML‑1 cells with low levels of KMO expression (KMOlow)]. Serum samples from 28 patients with DLBCL and 34 healthy volunteers were used to investigate the association between prognosis and KMO activity or 3‑HK levels. Furthermore, to investigate the roles of KMO and its related metabolites, STR‑428 and KML‑1 cell lines, and the lymph nodes of patients with DLBCL were analyzed by reverse transcription‑quantitative PCR for KMO, KYNU, 3‑hydroxyanthranilate‑3,4‑dioxygenase and quinolinate phosphoribosyltransferase, by western blotting, and immunohistochemical or immunofluorescence staining for KMO, and by cell viability and NAD+/NADH assays. KYN pathway metabolites in serum samples were measured by HPLC. Serum 3‑HK levels were regulated independently of serum KYN levels, and increased serum 3‑HK levels and KMO activity were found to be associated with worse disease progression. Notably, the addition of KMO inhibitors and 3‑HK negatively and positively regulated the viability of DLBCL cells, respectively. Furthermore, NAD+ levels in KMOhigh STR‑428 cells were significantly higher than those in KMOlow KML‑1 cells. These results suggested that 3‑HK generated by KMO activity may be involved in the regulation of DLBCL cell viability via NAD+ synthesis.
AD - Department of Disease Control and Prevention, Fujita Health University, Toyoake, Aichi 470-1192, Japan
Department of Biochemical and Analytical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan
First Department of Internal Medicine, Gifu University Graduate School of Medicine, Yanagido, Gifu 501-1194, Japan
Department of Hematology, Matsunami General Hospital, Kasamatsucho, Gifu 501-6062, Japan
Department of Educational Collaboration, Health and Safety Sciences, Osaka Kyoiku University, Kashiwara, Osaka 582-8285, Japan
Department of Pathology, Suzuka University of Medical Sciences, Suzuka, Mie 510-0293, Japan
AU - Morita,Nanaka
AU - Hoshi,Masato
AU - Hara,Takeshi
AU - Ninomiya,Soranobu
AU - Enoki,Taisuke
AU - Yoneda,Misao
AU - Tsurumi,Hisashi
AU - Saito,Kuniaki
DA - 2021/11/01
DO - 10.3892/ol.2021.13051
IS - 5
JO - Oncol Lett
KW - DLBCL
KMO
NAD+
3-HK
KYN pathway
PY - 2021
SN - 1792-1074
1792-1082
SP - 790
ST - Viability of diffuse large B-cell lymphoma cells is regulated by kynurenine 3-monooxygenase activity
T2 - Oncology Letters
TI - Viability of diffuse large B-cell lymphoma cells is regulated by kynurenine 3-monooxygenase activity
UR - https://doi.org/10.3892/ol.2021.13051
VL - 22
ER -