Flow cytometry-based photodynamic diagnosis with 5-aminolevulinic acid for the detection of minimal residual disease in multiple myeloma

Keita Iwaki, Tohru Fujiwara, Takako Ito, Chie Suzuki, Katsuyuki Sasaki, Koya Ono, Kei Saito, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Shinichi Fujimaki, Tohru Tanaka, Hideto Tamura, Minami Fujiwara, Hideo Harigae

Research output: Contribution to journalArticlepeer-review

Abstract

Multiple myeloma is the cancer of plasma cells. Along with the development of new and effective therapies, improved outcomes in patients with multiple myeloma have increased the interest in minimal residual disease (MRD) monitoring. However, the considerable heterogeneity of immunophenotypic and molecular markers of myeloma cells has limited its clinical application. 5-Aminolevulinic acid (ALA) is a natural compound in the heme biosynthesis pathway. Following ALA treatment, tumor cells preferentially accumulate porphyrins because of the differential activities of aerobic glycolysis, known as Warburg effect. Among various porphyrins, protoporphyrine IX is a strong photosensitizer; thus, ALA-based photodynamic diagnosis has been widely used in various solid cancers. Here, the feasibility of flow cytometry-based photodynamic detection of MRD was tested in multiple myeloma. Among various human cell lines of hematological malignancies, including K562 erythroleukemia, Jurkat T-cell leukemia, Nalm6 pre-B cell leukemia, KG1a myeloid leukemia, and U937 monocytic leukemia, human myeloma cell line, KMS18, and OPM2 abundantly expressed ALA transporters, such as SLC36A1 and SLC15A2, and 1 mM ALA treatment for 24 h resulted in nearly 100% porphyrin fluorescence expression, which could be competitively inhibited by ALA transport with gamma-aminobutyric acid. Titration studies revealed that the lowest ALA concentration required to achieve nearly 100% porphyrin fluorescence in KMS18 cells was 0.25 mM, with an incubation period of 2 h. Under these conditions, incubation of primary peripheral blood mononuclear cells resulted in only 1.8 % of the cells exhibiting porphyrin fluorescence. Therefore, flow cytometry-based photodynamic diagnosis is a promising approach for detecting MRD in multiple myeloma.

Original languageEnglish
Pages (from-to)19-28
Number of pages10
JournalTohoku Journal of Experimental Medicine
Volume249
Issue number1
DOIs
Publication statusPublished - 2019

Keywords

  • 5-aminolevulinic acid
  • Flow cytometry
  • Minimal residual disease
  • Multiple myeloma
  • Protoporphyrin ix

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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