Sensitive detection and apoptotic cell death induction of adult T-cell leukemia/lymphoma (ATL) cells with photodynamic actions

Abstract The 48-Kd cell-surface protein APO-1 is a new member of the nerve growth factor (NGF)/tumor necrosis factor (TNF) receptor superfamily. APO-1 is expressed on various cells, including activated T and B cells and some lymphoid and nonlymphoid cell lines. Triggering of APO-1 by the monoclonal antibody anti-APO-1 induces programmed cell death (apoptosis) in APO-1-expressing cells. APO-1 is also present on T-cell lines derived from patients with adult T-cell leukemia (ATL). Therefore, we investigated APO-1 expression and APO-1-mediated induction of apoptosis ex vivo in cells from patients with ATL. Fresh leukemic cells from nine patients with ATL were assayed for APO-1 expression by two-color immunofluorescence. The leukemic cells from all patients strongly expressed APO-1. Incubation of ATL cells with anti- APO-1 in vitro inhibited spontaneous and cytokine-mediated DNA synthesis. Furthermore, DNA isolated from cells treated with anti-APO-1 exhibited polynucleosomal DNA fragmentation (DNA ladder) characteristic for apoptotic cell death. The analysis of APO-1-mediated apoptosis may represent a new approach to the study of growth control in lymphoid malignancies. In addition, induction of apoptosis by administration of anti-APO-1 may represent a new therapeutic approach for aggressive T- cell malignancies such as ATL.

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APO-1-induced apoptosis of leukemia cells from patients with adult T- cell leukemia

Blood ◽

10.1182/blood.v81.11.2972.bloodjournal81112972 ◽

1993 ◽

Vol 81 (11) ◽

pp. 2972-2977 ◽

Cited By ~ 1

Author(s):

KM Debatin ◽

CK Goldman ◽

TA Waldmann ◽

PH Krammer

Keyword(s):

Cell Death ◽

T Cell ◽

Cell Lines ◽

Ex Vivo ◽

Apoptotic Cell ◽

Leukemic Cells ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Adult T Cell Leukemia ◽

Induction Of Apoptosis

The 48-Kd cell-surface protein APO-1 is a new member of the nerve growth factor (NGF)/tumor necrosis factor (TNF) receptor superfamily. APO-1 is expressed on various cells, including activated T and B cells and some lymphoid and nonlymphoid cell lines. Triggering of APO-1 by the monoclonal antibody anti-APO-1 induces programmed cell death (apoptosis) in APO-1-expressing cells. APO-1 is also present on T-cell lines derived from patients with adult T-cell leukemia (ATL). Therefore, we investigated APO-1 expression and APO-1-mediated induction of apoptosis ex vivo in cells from patients with ATL. Fresh leukemic cells from nine patients with ATL were assayed for APO-1 expression by two-color immunofluorescence. The leukemic cells from all patients strongly expressed APO-1. Incubation of ATL cells with anti- APO-1 in vitro inhibited spontaneous and cytokine-mediated DNA synthesis. Furthermore, DNA isolated from cells treated with anti-APO-1 exhibited polynucleosomal DNA fragmentation (DNA ladder) characteristic for apoptotic cell death. The analysis of APO-1-mediated apoptosis may represent a new approach to the study of growth control in lymphoid malignancies. In addition, induction of apoptosis by administration of anti-APO-1 may represent a new therapeutic approach for aggressive T- cell malignancies such as ATL.

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SRT1720 induces SIRT1‐independent cell death in adult T‐cell leukemia/lymphoma

FEBS Journal ◽

10.1111/febs.16353 ◽

2022 ◽

Author(s):

Tomohiro Kozako ◽

Naho Kato ◽

Takeo Ohsugi ◽

Yu‐ichiro Uchida ◽

Makoto Yoshimitsu ◽

...

Keyword(s):

Cell Death ◽

T Cell ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Adult T Cell Leukemia

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Cell death induced by dorsomorphin in adult T‐cell leukemia/lymphoma is AMPK‐independent

FEBS Journal ◽

10.1111/febs.15239 ◽

2020 ◽

Vol 287 (18) ◽

pp. 4005-4015

Author(s):

Akiyoshi Aikawa ◽

Tomohiro Kozako ◽

Yuichiro Uchida ◽

Makoto Yoshimitsu ◽

Kenji Ishitsuka ◽

...

Keyword(s):

Cell Death ◽

T Cell ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Adult T Cell Leukemia

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Relationship between triterpenoid anticancer drug resistance, autophagy, and caspase-1 in adult T-cell leukemia

PeerJ ◽

10.7717/peerj.2026 ◽

2016 ◽

Vol 4 ◽

pp. e2026 ◽

Cited By ~ 6

Author(s):

Tsukasa Nakanishi ◽

Yuan Song ◽

Cuiying He ◽

Duo Wang ◽

Kentaro Morita ◽

...

Keyword(s):

Drug Resistance ◽

Cell Death ◽

T Cell ◽

Cord Blood Transplantation ◽

B Cell Lymphoma ◽

Human Leukemia ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Adult T Cell Leukemia ◽

Caspase 1

We previously reported that the inflammasome inhibitor cucurbitacin D (CuD) induces apoptosis in human leukemia cell lines. Here, we investigated the effects of CuD and a B-cell lymphoma extra-large (Bcl-xL) inhibitor on autophagy in peripheral blood lymphocytes (PBL) isolated from adult T-cell leukemia (ATL) patients. CuD induced PBL cell death in patients but not in healthy donors. This effect was not significantly inhibited by treatment with rapamycin or 3-methyladenine (3-MA). The Bcl-xL inhibitor Z36 induced death in primary cells from ATL patients including that induced by CuD treatment, effects that were partly inhibited by 3-MA. Similarly, cell death induced by the steroid prednisolone was enhanced in the presence of Z36. A western blot analysis revealed that Z36 also promoted CuD-induced poly(ADP ribose) polymerase cleavage. Interestingly, the effects of CuD and Z36 were attenuated in primary ATL patient cells obtained upon recurrence after umbilical cord blood transplantation, as compared to those obtained before chemotherapy. Furthermore, cells from this patient expressed a high level of caspase-1, and treatment with caspase-1 inhibitor-enhanced CuD-induced cell death. Taken together, these results suggest that rescue from resistance to steroid drugs can enhance chemotherapy, and that caspase-1 is a good marker for drug resistance in ATL patients.

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Restoration of ceramide de novo synthesis by the synthetic retinoid ST1926 as it induces adult T-cell leukemia cell death

Bioscience Reports ◽

10.1042/bsr20200050 ◽

2020 ◽

Vol 40 (10) ◽

Author(s):

Botheina Ghandour ◽

Claudio Pisano ◽

Nadine Darwiche ◽

Ghassan Dbaibo

Keyword(s):

Cell Death ◽

T Cell ◽

De Novo ◽

Leukemia Cell ◽

T Cell Leukemia ◽

Ceramide Synthase ◽

Cell Leukemia ◽

Adult T Cell Leukemia ◽

Synthetic Retinoid ◽

Human T Cell

Abstract Ceramide (Cer) is a bioactive cellular lipid with compartmentalized and tightly regulated levels. Distinct metabolic pathways lead to the generation of Cer species with distinguishable roles in oncogenesis. Deregulation of Cer pathways has emerged as an important mechanism for acquired chemotherapeutic resistance. Adult T-cell leukemia (ATL) cells are defective in Cer synthesis. ATL is an aggressive neoplasm that develops following infection with human T-cell lymphotropic virus-1 (HTLV-1) where the viral oncogene Tax contributes to the pathogenesis of the disease. ATL cells, resistant to all-trans-retinoic acid, are sensitive to pharmacologically achievable concentrations of the synthetic retinoid ST1926. We studied the effects of ST1926 on Cer pathways in ATL cells. ST1926 treatment resulted in early Tax oncoprotein degradation in HTLV-1-treated cells. ST1926 induced cell death and a dose- and time-dependent accumulation of Cer in malignant T cells. The kinetics and degree of Cer production showed an early response upon ST1926 treatment. ST1926 enhanced de novo Cer synthesis via activation of ceramide synthase CerS(s) without inhibiting dihydroceramide desaturase, thereby accumulating Cer rather than the less bioactive dihydroceramide. Using labeling experiments with the unnatural 17-carbon sphinganine and measuring the generated Cer species, we showed that ST1926 preferentially induces the activities of a distinct set of CerS(s). We detected a delay in cell death response and interruption of Cer generation in response to ST1926 in Molt-4 cells overexpressing Bcl-2. These results highlight the potential role of ST1926 in inducing Cer levels, thus lowering the threshold for cell death in ATL cells.

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Sensitive Photodynamic Detection of Adult T-cell Leukemia/Lymphoma and Specific Leukemic Cell Death Induced by Photodynamic Therapy: Current Status in Hematopoietic Malignancies

Cancers ◽

10.3390/cancers12020335 ◽

2020 ◽

Vol 12 (2) ◽

pp. 335 ◽

Cited By ~ 2

Author(s):

Takashi Oka ◽

Ken-ichi Matsuoka ◽

Atae Utsunomiya

Keyword(s):

Cell Death ◽

Photodynamic Therapy ◽

T Cell ◽

Leukemic Cell ◽

Type I ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Cell Leukemia Virus Type ◽

Hematopoietic Malignancies ◽

Adult T Cell Leukemia

Adult T-cell leukemia/lymphoma (ATL), an aggressive type of T-cell malignancy, is caused by the human T-cell leukemia virus type I (HTLV-1) infections. The outcomes, following therapeutic interventions for ATL, have not been satisfactory. Photodynamic therapy (PDT) exerts selective cytotoxic activity against malignant cells, as it is considered a minimally invasive therapeutic procedure. In PDT, photosensitizing agent administration is followed by irradiation at an absorbance wavelength of the sensitizer in the presence of oxygen, with ultimate direct tumor cell death, microvasculature injury, and induced local inflammatory reaction. This review provides an overview of the present status and state-of-the-art ATL treatments. It also focuses on the photodynamic detection (PDD) of hematopoietic malignancies and the recent progress of 5-Aminolevulinic acid (ALA)-PDT/PDD, which can efficiently induce ATL leukemic cell-specific death with minor influence on normal lymphocytes. Further consideration of the ALA-PDT/PDD system along with the circulatory system regarding the clinical application in ATL and others will be discussed. ALA-PDT/PDD can be promising as a novel treatment modality that overcomes unmet medical needs with the optimization of PDT parameters to increase the effectiveness of the tumor-killing activity and enhance the innate and adaptive anti-tumor immune responses by the optimized immunogenic cell death.

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