Prognostic significance of tryptophan catabolism in adult T-cell leukemia/lymphoma

Ayako Masaki; Takashi Ishida; Yasuhiro Maeda; Susumu Suzuki; Asahi Ito; Hisashi Takino; Haruhito Totani; Takashi Yoshida; Shiori Kinoshita; Hiroka Ogura; Tomoko Narita; Masaki Ri; Shigeru Kusumoto; Atsushi Inagaki; Hirokazu Komatsu; Akio Niimi; Ryuzo Ueda; Atae Utsunomiya; Hiroshi Inagaki; Shinsuke Iida

doi:10.11406/rinketsu.56.2295

Prognostic significance of tryptophan catabolism in adult T-cell leukemia/lymphoma

Ayako Masaki
, Takashi Ishida
, Yasuhiro Maeda
, Susumu Suzuki
, Asahi Ito
, Hisashi Takino
, Haruhito Totani
, Takashi Yoshida
, Shiori Kinoshita
, Hiroka Ogura
, Tomoko Narita
, Masaki Ri
, Shigeru Kusumoto
, Atsushi Inagaki
, Hirokazu Komatsu
, Akio Niimi
, Ryuzo Ueda
, Atae Utsunomiya
, Hiroshi Inagaki
, Shinsuke Iida

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

PURPOSE: Indoleamine 2,3-dioxygenase 1 (IDO1: IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway, and is an important micro-environmental factor suppressing antitumor immune responses. We investigated the prognostic significance of Trp catabolism in adult T-cell leukemia/lymphoma (ATL).

EXPERIMENTAL DESIGN: We quantified serum Trp and Kyn in 96 ATL patients, 38 human T-cell lymphotropic virus type-1 asymptomatic carriers (HTLV-1 ACs), and 40 healthy adult volunteers. The relationships between various clinical parameters were analyzed. IDO expression was evaluated in the affected lymph nodes of ATL patients.

RESULTS: Serum Kyn concentrations and Kyn/Trp ratios were significantly higher in HTLV-1 ACs than in healthy controls. Both increased significantly with progression from HTLV-1 AC to ATL. There were no significant differences in serum Trp concentrations between ATL patients, HTLV-1 ACs and controls. IDO was possibly produced by ATL and/or cells in the microenvironment. Multivariate analyses demonstrated a high serum Kyn/Trp ratio and high Kyn level, but not a high Trp level, to be significant independent detrimental prognostic factors in ATL and aggressive variant ATL.

CONCLUSIONS: Quantification of serum Kyn and Trp is prognostically useful for individual ATL patients. Furthermore, ATL is an appropriate disease for testing novel cancer immunotherapies targeting IDO.

Original language	English
Pages (from-to)	2295-2304
Number of pages	10
Journal	[Rinshō ketsueki] The Japanese journal of clinical hematology
Volume	56
Issue number	11
DOIs	https://doi.org/10.11406/rinketsu.56.2295
Publication status	Published - 01-11-2015
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.11406/rinketsu.56.2295

Cite this

Masaki, A., Ishida, T., Maeda, Y., Suzuki, S., Ito, A., Takino, H., Totani, H., Yoshida, T., Kinoshita, S., Ogura, H., Narita, T., Ri, M., Kusumoto, S., Inagaki, A., Komatsu, H., Niimi, A., Ueda, R., Utsunomiya, A., Inagaki, H., & Iida, S. (2015). Prognostic significance of tryptophan catabolism in adult T-cell leukemia/lymphoma. [Rinshō ketsueki] The Japanese journal of clinical hematology, 56(11), 2295-2304. https://doi.org/10.11406/rinketsu.56.2295

@article{c690b8da132b48ae915875fa2cb1b87d,

title = "Prognostic significance of tryptophan catabolism in adult T-cell leukemia/lymphoma",

abstract = "PURPOSE: Indoleamine 2,3-dioxygenase 1 (IDO1: IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway, and is an important micro-environmental factor suppressing antitumor immune responses. We investigated the prognostic significance of Trp catabolism in adult T-cell leukemia/lymphoma (ATL).EXPERIMENTAL DESIGN: We quantified serum Trp and Kyn in 96 ATL patients, 38 human T-cell lymphotropic virus type-1 asymptomatic carriers (HTLV-1 ACs), and 40 healthy adult volunteers. The relationships between various clinical parameters were analyzed. IDO expression was evaluated in the affected lymph nodes of ATL patients.RESULTS: Serum Kyn concentrations and Kyn/Trp ratios were significantly higher in HTLV-1 ACs than in healthy controls. Both increased significantly with progression from HTLV-1 AC to ATL. There were no significant differences in serum Trp concentrations between ATL patients, HTLV-1 ACs and controls. IDO was possibly produced by ATL and/or cells in the microenvironment. Multivariate analyses demonstrated a high serum Kyn/Trp ratio and high Kyn level, but not a high Trp level, to be significant independent detrimental prognostic factors in ATL and aggressive variant ATL.CONCLUSIONS: Quantification of serum Kyn and Trp is prognostically useful for individual ATL patients. Furthermore, ATL is an appropriate disease for testing novel cancer immunotherapies targeting IDO.",

author = "Ayako Masaki and Takashi Ishida and Yasuhiro Maeda and Susumu Suzuki and Asahi Ito and Hisashi Takino and Haruhito Totani and Takashi Yoshida and Shiori Kinoshita and Hiroka Ogura and Tomoko Narita and Masaki Ri and Shigeru Kusumoto and Atsushi Inagaki and Hirokazu Komatsu and Akio Niimi and Ryuzo Ueda and Atae Utsunomiya and Hiroshi Inagaki and Shinsuke Iida",

year = "2015",

month = nov,

day = "1",

doi = "10.11406/rinketsu.56.2295",

language = "English",

volume = "56",

pages = "2295--2304",

journal = "[Rinshō ketsueki] The Japanese journal of clinical hematology",

issn = "0485-1439",

publisher = "Nihon Rinsho Ketsueki Gakkai/Japan Society of Clinical Hematology",

number = "11",

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Masaki, A, Ishida, T, Maeda, Y, Suzuki, S, Ito, A, Takino, H, Totani, H, Yoshida, T, Kinoshita, S, Ogura, H, Narita, T, Ri, M, Kusumoto, S, Inagaki, A, Komatsu, H, Niimi, A, Ueda, R, Utsunomiya, A, Inagaki, H & Iida, S 2015, 'Prognostic significance of tryptophan catabolism in adult T-cell leukemia/lymphoma', [Rinshō ketsueki] The Japanese journal of clinical hematology, vol. 56, no. 11, pp. 2295-2304. https://doi.org/10.11406/rinketsu.56.2295

TY - JOUR

T1 - Prognostic significance of tryptophan catabolism in adult T-cell leukemia/lymphoma

AU - Masaki, Ayako

AU - Ishida, Takashi

AU - Maeda, Yasuhiro

AU - Suzuki, Susumu

AU - Ito, Asahi

AU - Takino, Hisashi

AU - Totani, Haruhito

AU - Yoshida, Takashi

AU - Kinoshita, Shiori

AU - Ogura, Hiroka

AU - Narita, Tomoko

AU - Ri, Masaki

AU - Kusumoto, Shigeru

AU - Inagaki, Atsushi

AU - Komatsu, Hirokazu

AU - Niimi, Akio

AU - Ueda, Ryuzo

AU - Utsunomiya, Atae

AU - Inagaki, Hiroshi

AU - Iida, Shinsuke

PY - 2015/11/1

Y1 - 2015/11/1

N2 - PURPOSE: Indoleamine 2,3-dioxygenase 1 (IDO1: IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway, and is an important micro-environmental factor suppressing antitumor immune responses. We investigated the prognostic significance of Trp catabolism in adult T-cell leukemia/lymphoma (ATL).EXPERIMENTAL DESIGN: We quantified serum Trp and Kyn in 96 ATL patients, 38 human T-cell lymphotropic virus type-1 asymptomatic carriers (HTLV-1 ACs), and 40 healthy adult volunteers. The relationships between various clinical parameters were analyzed. IDO expression was evaluated in the affected lymph nodes of ATL patients.RESULTS: Serum Kyn concentrations and Kyn/Trp ratios were significantly higher in HTLV-1 ACs than in healthy controls. Both increased significantly with progression from HTLV-1 AC to ATL. There were no significant differences in serum Trp concentrations between ATL patients, HTLV-1 ACs and controls. IDO was possibly produced by ATL and/or cells in the microenvironment. Multivariate analyses demonstrated a high serum Kyn/Trp ratio and high Kyn level, but not a high Trp level, to be significant independent detrimental prognostic factors in ATL and aggressive variant ATL.CONCLUSIONS: Quantification of serum Kyn and Trp is prognostically useful for individual ATL patients. Furthermore, ATL is an appropriate disease for testing novel cancer immunotherapies targeting IDO.

AB - PURPOSE: Indoleamine 2,3-dioxygenase 1 (IDO1: IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway, and is an important micro-environmental factor suppressing antitumor immune responses. We investigated the prognostic significance of Trp catabolism in adult T-cell leukemia/lymphoma (ATL).EXPERIMENTAL DESIGN: We quantified serum Trp and Kyn in 96 ATL patients, 38 human T-cell lymphotropic virus type-1 asymptomatic carriers (HTLV-1 ACs), and 40 healthy adult volunteers. The relationships between various clinical parameters were analyzed. IDO expression was evaluated in the affected lymph nodes of ATL patients.RESULTS: Serum Kyn concentrations and Kyn/Trp ratios were significantly higher in HTLV-1 ACs than in healthy controls. Both increased significantly with progression from HTLV-1 AC to ATL. There were no significant differences in serum Trp concentrations between ATL patients, HTLV-1 ACs and controls. IDO was possibly produced by ATL and/or cells in the microenvironment. Multivariate analyses demonstrated a high serum Kyn/Trp ratio and high Kyn level, but not a high Trp level, to be significant independent detrimental prognostic factors in ATL and aggressive variant ATL.CONCLUSIONS: Quantification of serum Kyn and Trp is prognostically useful for individual ATL patients. Furthermore, ATL is an appropriate disease for testing novel cancer immunotherapies targeting IDO.

UR - https://www.scopus.com/pages/publications/84979792357

UR - https://www.scopus.com/pages/publications/84979792357#tab=citedBy

U2 - 10.11406/rinketsu.56.2295

DO - 10.11406/rinketsu.56.2295

M3 - Article

C2 - 26666715

AN - SCOPUS:84979792357

SN - 0485-1439

VL - 56

SP - 2295

EP - 2304

JO - [Rinshō ketsueki] The Japanese journal of clinical hematology

JF - [Rinshō ketsueki] The Japanese journal of clinical hematology

IS - 11

ER -

Prognostic significance of tryptophan catabolism in adult T-cell leukemia/lymphoma

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