Metabolic abnormalities in adult T-cell leukemia/lymphoma and induction of specific leukemic cell death using photodynamic therapy

Takashi Oka, Hajime Mizuno, Masumi Sakata, Hirofumi Fujita, Tadashi Yoshino, Yoshihisa Yamano, Kozo Utsumi, Tsutomu Masujima, Atae Utsunomiya

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number14979
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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Adult T Cell Leukemia Lymphoma
Photochemotherapy
Cell Death
Human T-lymphotropic virus 1
Metabolic Networks and Pathways
Blood Cells
Aminolevulinic Acid
Metabolomics
Porphyrins
Virus Diseases
Cardiovascular System
Flow Cytometry
T-Lymphocytes
Light
Therapeutics

ASJC Scopus subject areas

  • General

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Metabolic abnormalities in adult T-cell leukemia/lymphoma and induction of specific leukemic cell death using photodynamic therapy. / Oka, Takashi; Mizuno, Hajime; Sakata, Masumi; Fujita, Hirofumi; Yoshino, Tadashi; Yamano, Yoshihisa; Utsumi, Kozo; Masujima, Tsutomu; Utsunomiya, Atae.

In: Scientific Reports, Vol. 8, No. 1, 14979, 01.12.2018.

Research output: Contribution to journalArticle

Oka, Takashi ; Mizuno, Hajime ; Sakata, Masumi ; Fujita, Hirofumi ; Yoshino, Tadashi ; Yamano, Yoshihisa ; Utsumi, Kozo ; Masujima, Tsutomu ; Utsunomiya, Atae. / Metabolic abnormalities in adult T-cell leukemia/lymphoma and induction of specific leukemic cell death using photodynamic therapy. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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