Quantification of adult T-cell leukemia/lymphoma cells using simple four-color flow cytometry

Ishigaki, Tomohiro; Zaike, Yuji; Nojima, Masanori; Kobayashi, Seiichiro; Ohno, Nobuhiro; Uchimaru, Kaoru; Tojo, Arinobu; Nakauchi, Hiromitsu; Watanabe, Nobuyuki

doi:10.1515/cclm-2014-0183

Cited by 5 publications

(11 citation statements)

References 7 publications

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“…HAS Flow method has been established, showing that the proportion of TSLC1 + subpopulations (TSLC1 pos CD7 dim and TSLC1 pos CD7 neg ) increased with the progression from AC to indolent and to aggressive ATL. This analysis identified the putative high risk AC and also the intermediate stage of ATL progression 51 , 52 . In the present study, ALA-PDT successfully induced 98.7% of ATL leukemic cell death with minimal damage on the healthy PBMCs in chronic ATL patient specimen, implying that ALA-PDT effectively inhibit the progression from indolent to aggressive ATL in addition to identification of intermediate stage of progression in ATL (Figs 5 and 6 ).…”

Section: Discussionmentioning

confidence: 99%

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

Oka

Mizuno

Sakata³

et al. 2018

Sci Rep

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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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Section: Discussionmentioning

confidence: 99%

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

Oka

Mizuno

Sakata³

et al. 2018

Sci Rep

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“…The serum levels of soluble interleukin‐2 receptor (sIL‐2R) were collected from medical records. The percentages of abnormal lymphocytes in white blood cells were counted microscopically by clinical laboratory technicians as previously described . The HTLV‐1 PVL data were obtained from the Joint Study on Predisposing Factors of ATL Development (JSPFAD) .…”

Section: Methodsmentioning

confidence: 99%

CD4⁺CADM1⁺ cell percentage predicts disease progression in HTLV‐1 carriers and indolent adult T‐cell leukemia/lymphoma

et al. 2019

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We recently took advantage of the universal expression of cell adhesion molecule 1 (CADM1) by CD4 + cells infected with HTLV-1 and the downregulation of CD7 expression that corresponds with the oncogenic stage of HTLV-1-infected cells to develop a flow cytometric system using CADM1 versus CD7 plotting of CD4 + cells. We risk-stratified HTLV-1 asymptomatic carriers (AC) and indolent adult T-cell leukemia/ lymphoma (ATL) cases based on the CADM1 + percentage, in which HTLV-1-infected clones are efficiently enriched. AC and indolent ATL cases were initially classified according to their CADM1 + cell percentage. Follow-up clinical and flow cytometric data were obtained for 71 cases. In G1 (CADM1 + ≤ 10%) and G2 (10% < CADM1 + ≤ 25%) cases, no apparent clinical disease progression was observed. In G3 (25% < CADM1 + ≤ 50%) cases, five out of nine (55.5%) cases progressed from AC to smoldering-type ATL. In G4 (50% < CADM1 + ) cases, the cumulative incidence of receiving systemic chemotherapy at 3 years was 28.4%. Our results indicate that the percentage of the CD4 + CADM1 + population predicts clinical disease progression: G1 and G2 cases, including AC cases, are stable and considered to be at low risk; G3 cases, including advanced AC cases and smoldering-type ATL cases based on the Shimoyama criteria, are considered to have intermediate risk; and G4 cases, which are mainly indolent ATL cases, are unstable and at high risk of acute transformation. K E Y W O R D Sasymptomatic carriers, ATL, CADM1, flow cytometry, HTLV-1

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“…Clinically, ATL is characterized by high frequency of skin rashes. In most cases, circulating tumor cells in this disease are characterized by CD4 + CD7 − immunophenotypes (Ishigaki et al, 2015). Therefore, the clinical course of this disease can be followed by the monitoring of the proportion of CD4 + CD7 − T cells (Ishigaki et al, 2015).…”

Section: Adult T-cell Leukemia/lymphoma (Atl)mentioning

confidence: 99%

“…In most cases, circulating tumor cells in this disease are characterized by CD4 + CD7 − immunophenotypes (Ishigaki et al, 2015). Therefore, the clinical course of this disease can be followed by the monitoring of the proportion of CD4 + CD7 − T cells (Ishigaki et al, 2015). In addition, it was reported that the number of CD3 dim CD4 + CD7 low were increased significantly in acute-type ATL.…”

Section: Adult T-cell Leukemia/lymphoma (Atl)mentioning

confidence: 99%

“…It seems that through production of several cytokines such as IL-4 and IL-10, CD4 + CD7 − T cells play a key role in the pathogenesis of the disease because such cytokines are unable to induce effective antitumor immune responses (Autran, Legac, Blanc, & Debre, 1995). In addition, patients with dropped CD4 + CD7 − T cells proportion after chemotherapy have better prognosis (Ishigaki et al, 2015). So, these cells could be considered as potential therapy for the treatment of diseases.…”

Section: Adult T-cell Leukemia/lymphoma (Atl)mentioning

confidence: 99%

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The clinical importance of CD4⁺CD7⁻ in human diseases

Haftcheshmeh

Tajbakhsh

Kazemi

et al. 2018

Journal Cellular Physiology

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The CD7 antigen is a member of the immunoglobulin superfamily that expresses on the surface of all thymocytes, a majority of mature T cells, and also natural killer cells. Interestingly, under physiological and different pathological conditions, the loss of CD7 antigen occurred in the subset of CD4 memory T cells. Various functions have been proposed for CD7, including its role in the activation and intercellular adhesiveness of T cells. Several studies indicate that the number of CD4 CD7 T cells increases in diseases such as chronic inflammation and T-cell malignancies, these being skin inflammatory lesions. Therefore, this can be useful for the diagnosis of cancer cells, especially with reference to blood origin, treatment monitoring, and establishment of new therapies. Therefore, a comprehensive review could be useful to increase our knowledge about the clinical importance of these cells in human disease.

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Quantification of adult T-cell leukemia/lymphoma cells using simple four-color flow cytometry

Abstract: Our newly established method quantified tumor cells in patients with acute-type ATL. Furthermore, this method was useful for assessing the efficacy of chemotherapy, and the change of the CD7N proportion could be more important to predict prognosis.

Cited by 5 publications

References 7 publications

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

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

CD4⁺CADM1⁺ cell percentage predicts disease progression in HTLV‐1 carriers and indolent adult T‐cell leukemia/lymphoma

The clinical importance of CD4⁺CD7⁻ in human diseases

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Quantification of adult T-cell leukemia/lymphoma cells using simple four-color flow cytometry

Abstract: Our newly established method quantified tumor cells in patients with acute-type ATL. Furthermore, this method was useful for assessing the efficacy of chemotherapy, and the change of the CD7N proportion could be more important to predict prognosis.

Cited by 5 publications

References 7 publications

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

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

CD4+CADM1+ cell percentage predicts disease progression in HTLV‐1 carriers and indolent adult T‐cell leukemia/lymphoma

The clinical importance of CD4+CD7− in human diseases

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CD4⁺CADM1⁺ cell percentage predicts disease progression in HTLV‐1 carriers and indolent adult T‐cell leukemia/lymphoma

The clinical importance of CD4⁺CD7⁻ in human diseases