CD158k/KIR3DL2 Is a New Phenotypic Marker of Sezary Cells: Relevance for the Diagnosis and Follow-Up of Sezary Syndrome

Sezary syndrome (SS) is a rare leukemic form of cutaneous T-cell lymphoma. Diagnosis mainly depends on flow cytometry, but results are not specific enough to be unequivocal. The difficulty in defining a single marker that could characterize Sezary cells may be the consequence of different pathological subtypes. In this study, we used multivariate flow cytometry analyses. We chose to investigate the expression of classical CD3, CD4, CD7, and CD26 and the 2 new association of 2 markers CD158k and PD-1. We performed lymphocyte computational phenotypic analyses during diagnosis and follow-up of SS patients to define new SS classes and improve the sensitivity of the diagnosis and the follow-up flow cytometry method. Three classes of SS, defined by different immunophenotypic profiles, CD158k-positive SS, CD158k-negative PD-1-positive SS, CD158k and PD-1 double-negative SS, showed different CD8+ and B-cells environments. Such a study could help to diagnose and define biological markers of susceptibility/resistance to treatment including immunotherapy. -

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Mycosis fungoides and Sézary syndrome: a population-wide study on prevalence and health care use in Finland in 1998–2016

BMC Health Services Research ◽

10.1186/s12913-021-06109-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jaana Keto ◽

Sonja Hahtola ◽

Miika Linna ◽

Liisa Väkevä

Keyword(s):

Health Care ◽

Mycosis Fungoides ◽

Hospital Costs ◽

Fold Increase ◽

Medical Specialty ◽

Health Care Use ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Outpatient Visits

Abstract Background Information about health care use and costs of cutaneous T-cell lymphoma (CTCL) patients is limited, particularly in a European setting. Methods In this population-wide study we set out to investigate prevalence, and trends in health care use in two CTCL subtypes, mycosis fungoides (MF) and Sézary syndrome (SS) over a time period of 19 years in 1998–2016 by using a nation-wide patient register containing data on all diagnosed MF and SS cases in Finland. Results The prevalence of diagnosed MF and SS rose from 2.04 to 5.38/100000, and from 0.16 to 0.36/100000 for MF and SS respectively during 1998–2016. We found a substantial decrease in inpatient treatment of MF/SS in the past two decades with a mean of 2 inpatient days/patient/year due to MF/SS in 2016, while the mean numbers of MF/SS related outpatient visits remained stable at 8 visits/year/patient. Most MF/SS-related outpatient visits occurred in the medical specialty of dermatology. In a ten-year follow-up after MF/SS diagnosis, the main causes for outpatient visits and inpatient stays were MF/SS itself, other cancers, and other skin conditions. Also cardiovascular disease and infections contributed to the number of inpatient days. Mean total hospital costs decreased from 11,600 eur/patient/year to 3600 eur/patient/year by year 4 of the follow-up, and remained at that level for the remainder of the 10-year follow-up. MF/SS accounted for approximately half of the hospital costs of these patients throughout the follow-up. Conclusions The nearly 3-fold increase in prevalence of diagnosed MF/SS during 1998–2016 puts pressure on the health care system, as this is a high-cost patient group with a heavy burden of comorbidities. The challenge can be in part answered by shifting the treatment of MF/SS to a more outpatient-based practice, and by adapting new pharmacotherapy, as has been done in Finland.

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The Role of Tumor Microenvironment in the Pathogenesis of Sézary Syndrome

International Journal of Molecular Sciences ◽

10.3390/ijms23020936 ◽

2022 ◽

Vol 23 (2) ◽

pp. 936

Author(s):

Denis Miyashiro ◽

Bruno de Castro e Souza ◽

Marina Passos Torrealba ◽

Kelly Cristina Gomes Manfrere ◽

Maria Notomi Sato ◽

...

Keyword(s):

Tumor Microenvironment ◽

Immune Dysregulation ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Immunologic Response ◽

T Cell Lymphomas ◽

Sézary Cells ◽

Peripheral Blood Involvement ◽

Malignant T Cells

Sézary syndrome is an aggressive leukemic variant of cutaneous T-cell lymphomas, characterized by erythroderma, lymphadenopathy, and peripheral blood involvement by CD4+ malignant T-cells. The pathogenesis of Sézary syndrome is not fully understood. However, the course of the disease is strongly influenced by the tumor microenvironment, which is altered by a combination of cytokines, chemokines, and growth factors. The crosstalk between malignant and reactive cells affects the immunologic response against tumor cells causing immune dysregulation. This review focuses on the interaction of malignant Sézary cells and the tumor microenvironment.

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Stable Suppression of a Novel Oncogene, AHI-1, in Human Cutaneous T-Cell Leukemia Cells Normalizes Its Transforming Activity In Vitro and In Vivo and Aberrant Expression of AHI-1 Is Also Present in Leukemic Sezary Cells from Patients with Sezary Syndrome.

Blood ◽

10.1182/blood.v106.11.2605.2605 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2605-2605

Author(s):

Ashley Ringrose ◽

Youwen Zhou ◽

Emily Pang ◽

Ann E.-J. Lin ◽

Xiao-Jiang Li ◽

...

Keyword(s):

T Cell ◽

Leukemia Cell ◽

Leukemic Cells ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Cell Leukemia ◽

Rt Pcr ◽

Leukemia Cell Lines ◽

Semi Solid ◽

Sézary Cells

Abstract Ahi-1 (Abelson helper integration site 1) is a novel gene that is commonly activated by provirus insertional mutagenesis in v-abl and myc-induced murine leukemias and lymphomas. It encodes a unique protein with SH3 and WD40-repeat domains suggesting novel signaling activities. Involvement of Ahi-1 in leukemogenesis is suggested by the high frequency of Ahi-1 mutations seen in certain virus-induced murine leukemias and lymphomas and by the gross perturbations seen in the expression of human AHI-1 and its isoforms in several human leukemia cell lines, particularly in the cutaneous T-cell leukemia cell lines, Hut 78 and Hut 102, where increases in AHI-1 transcripts of 40-fold are seen. To test directly whether the deregulated expression of AHI-1 in leukemic cells contributes to their transformed properties, knockdown of AHI-1 expression in Hut 78 cells, a cell line derived from peripheral blood of a patient with Sezary syndrome, was performed using retroviral-mediated RNA interference (RNAi). In a screen of 9 constructs that produce specific short hairpin AHI-1 transcripts, one was found to specifically inhibit AHI-1 expression in transduced Hut 78 cells by 80%, as evaluated by quantitative real-time RT-PCR, Northern and Western blot analyses. Retroviral-mediated suppression of AHI-1 also reduced the autocrine production of IL-2, IL-4 and TNFalpha in Hut 78 cells by up to 85% and caused a significant reduction in their growth factor independence in semi-solid cultures (up to 10-fold) and in single cell cultures (4-fold) by comparison to cells transduced with a control vector. Interestingly, although addition of IL-4, TNFalpha or a combination of 3 growth factors restored colony formation from the shRNA-transduced Hut 78 cells in semi-solid cultures, this was not achieved if only IL-2 was added, even though AHI-1 expression was inhibited. The ability of Hut 78 cells to produce tumors in NOD/SCID-β2microglobulin−/− mice within 3 weeks was also lost when AHI-1 expression was suppressed. Microarray analysis on RNA from Hut 78 cells with the suppression of AHI-1, using the Affymetrix Human Genome U133 plus 2.0 Arrays, identified differentially expressed molecules critical in T-cell activation, signal transduction, as well as cell proliferation and differentiation. Q-RT-PCR analysis revealed that the transcript levels of AHI-1 and its isoforms were significantly increased in CD4+CD7− Sezary cells, in which more than 85% of these cells are leukemic cells, in 5 of 6 blood samples obtained from patients with Sezary syndrome as compared to T cells similarly isolated from 8 healthy individuals. Elevated AHI-1 transcript levels were not found in 3 patient samples containing less than 35% leukemic Sezary cells. Taken together, these findings provide strong evidence of the oncogenic activity of AHI-1 in human T-cell leukemic cells and its deregulation can contribute to the development of human cutaneous T-cell lymphomas, including Sezary syndrome.

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Characteristics and Survival of 29 Patients with Sezary Syndrome.

Blood ◽

10.1182/blood.v106.11.5587.5587 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5587-5587

Author(s):

Francesca Sampogna ◽

Marina Frontani ◽

Giannandrea Baliva ◽

Damiano Abeni ◽

Giuseppe A. Lombardo ◽

...

Keyword(s):

Survival Analysis ◽

Survival Time ◽

White Blood Cells ◽

Clinical History ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Term Survival ◽

Kaplan Meier

Abstract We created a relational database of patients with cutaneous T-cell lymphoma (CTCL) to collect in a standardised fashion, anagraphic variables, clinical history, clinical, histological, haematological, and immunological information on CTCL patients hospitalised at IDI-IRCCS, Rome, Italy. At present, there are data on 424 patients, hospitalised from 1983 to July 2005. Active follow-up is performed yearly to ensure a standardised ascertainment of survival time. For deceased patients, the actual date of death (for all causes) is recorded, while surviving patients are censored at the date of last contact. The database includes 29 patients with Sezary syndrome (SS). Follow-up times ranged from 0 to 105 months. At first hospitalisation the median values of cells/mL were: white blood cells (WBC) 8750, neutrophils 4250, eosinophils 140, basophils 120, lymphocytes 2760, monocytes 500, CD3+ 2780, CD4+ 2431, CD8+ 192, CD19+ 96. Seventeen patients were deceased. We included in the Kaplan-Meier survival analysis only patients who were diagnosed before July 2004 (n=26). Median survival time from diagnosis was 52 months. No significant differences were observed in mortality for WBC (cutoff 9000 cells/uL), neutrophils (cutoff 4500 cells/uL), basophils (cutoff 200 cells/uL), lymphocytes (cutoff 3000 cells/uL), monocytes (cutoff 500 cells/uL), CD3+ (cutoff 2000 cells/uL), CD4+ (cutoff 2000 cells/uL), CD8+ (cutoff 200 cells/uL), CD19+ (cutoff 70 cells/uL). A lower survival was observed for patients with eosinophils <200 cells/uL (p=.08). Survival in patients with SS does not seem to be influenced by haemathologic parameters. However, patients with long-term survival (>90 months) are observed, and their characteristics should be further investigated. Survival analysis of 26 patients with Sézary syndrome, Rome, Italy, 1991–2004. Survival analysis of 26 patients with Sézary syndrome, Rome, Italy, 1991–2004.

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