TY - JOUR
T1 - Metabolic abnormalities in adult T-cell leukemia/lymphoma and induction of specific leukemic cell death using photodynamic therapy
AU - Oka, Takashi
AU - Mizuno, Hajime
AU - Sakata, Masumi
AU - Fujita, Hirofumi
AU - Yoshino, Tadashi
AU - Yamano, Yoshihisa
AU - Utsumi, Kozo
AU - Masujima, Tsutomu
AU - Utsunomiya, Atae
N1 - Funding Information:
The authors gratefully acknowledge Dr. M. Maeda and Dr. M Matsuoka from the Institute for Virus Research, Kyoto University, Japan; Dr. H. Oono from the Kyoto University Medical School, Japan; Dr. Y. Matsuo from the Fujisaki Cell Centre, Hayashibara Biochemical Labs, Inc., Okayama, Japan; the Health Science Research Resources Bank (Japan); the American Type Culture Collection (ATCC), USA; and the RIKEN BioResource Centre, Tsukuba, Japan for kindly providing the cell lines. The authors would also like to acknowledge Prof. M. Yamada (Department of Virology, Okayama University Medical School) and Prof. T. Yoshino (Department of Pathology & Oncology, Okayama University Medical School) for kindly permitting us to use their laboratory facilities and for the encouragement they provided. We also thank Mr. H. Okamoto and Mr. K. Isomoto from the Central Research Laboratory, Okayama University Medical School; and Ms. M. Shiotani from the Department of Pathology, Okayama University Medical School for their excellent technical support. This work was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) (T.O.) (grant no. 22590312 and 25460437). The data that support the findings of this study are available from the corresponding author upon reasonable request. The detailed clinical data are not publicly available due to them containing information that could compromise research participant privacy/consent.
Funding Information:
Competing Interests: Takashi Oka declares research funding from Otsuka Electronics Co., Ltd, Japan. The sponsor had no control over the interpretation, writing, or publication of this work. The other authors have no conflict of interest. A patent was issued. Patent applicant: Okayama University; Name of inventors: T. Oka, H. Fujita and T. Yoshino; Patent number: 6352912; Specific aspect of manuscript covered in patent application: The machine and methods based on the findings.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasm caused by human T-cell leukemia virus type I (HTLV-I). Therapeutic interventions have not been associated with satisfactory outcomes. We showed that the porphyrin metabolic pathway preferentially accumulates the endogenous photosensitive metabolite, protoporphyrin IX (PpIX) in ATL, after a short-term culture with 5-aminolevulinic acid (ALA). PpIX accumulated 10–100-fold more in ATL leukemic cells when compared to healthy peripheral blood mononuclear cells (PBMCs). Patient specimens showed dynamic changes in flow cytometry profiles during the onset and progression of ATL. Furthermore, 98.7% of ATL leukemic cell death in the ATL patient specimens could be induced with 10 min of visible light exposure, while 77.5% of normal PBMCs survived. Metabolomics analyses revealed that a specific stage of the metabolic pathway progressively deteriorated with HTLV-I infection and at the onset of ATL. Therefore, this method will be useful in diagnosing and identifying high-risk HTLV-I carriers with single cell resolutions. Photodynamic therapy in the circulatory system may be a potential treatment due to its highly-specific, non-invasive, safe, simultaneous, and repeatedly-treatable modalities.
AB - Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasm caused by human T-cell leukemia virus type I (HTLV-I). Therapeutic interventions have not been associated with satisfactory outcomes. We showed that the porphyrin metabolic pathway preferentially accumulates the endogenous photosensitive metabolite, protoporphyrin IX (PpIX) in ATL, after a short-term culture with 5-aminolevulinic acid (ALA). PpIX accumulated 10–100-fold more in ATL leukemic cells when compared to healthy peripheral blood mononuclear cells (PBMCs). Patient specimens showed dynamic changes in flow cytometry profiles during the onset and progression of ATL. Furthermore, 98.7% of ATL leukemic cell death in the ATL patient specimens could be induced with 10 min of visible light exposure, while 77.5% of normal PBMCs survived. Metabolomics analyses revealed that a specific stage of the metabolic pathway progressively deteriorated with HTLV-I infection and at the onset of ATL. Therefore, this method will be useful in diagnosing and identifying high-risk HTLV-I carriers with single cell resolutions. Photodynamic therapy in the circulatory system may be a potential treatment due to its highly-specific, non-invasive, safe, simultaneous, and repeatedly-treatable modalities.
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U2 - 10.1038/s41598-018-33175-7
DO - 10.1038/s41598-018-33175-7
M3 - Article
C2 - 30297858
AN - SCOPUS:85054599782
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 14979
ER -
