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 to 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 and dynamically deteriorated with HTLV-I infection and at the onset of ATL. Therefore, this method will be useful for diagnosing and identifying high-risk HTLV-I carriers and high-risk indolent ATL who appeared to have developed or were likely to develop the aggressive subtypes 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.
Takashi Oka received Ph.D., Graduate School of Engineering Science, Dept. of Biophysical Engineering, Osaka University, Japan in 1983 and DMSc (Doctor of Medical Science), Kochi Medical School, Japan in 1992. He was appointed Assistant professor, Department of Pathology, Kochi Medical School in 1983 and Visiting Scientist, Department of Tumor Virology, Research Institute for Microbial Diseases, Osaka University (1983-1984). He researched in Department of Molecular Pathology, M.D. Anderson Cancer Center, The University of Texas, USA as a Visiting Assistant Professor (1992-1994) and became Visiting Scientist, Department of Cancer Biology, Harvard AIDS Institute, Harvard University, Boston, MA, USA (1994-1996). Then, he was appointed Assistant Professor, Department of Pathology, Okayama University Medical School 1996 and was promoted to Lecturer, Department of Pathology and Oncology, Okayama University from 2015.and Lecturer, Department of Hematology, Oncology and Respiratory Medicine Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University from 2019.