The biomarker landscape in mycosis fungoides and Sézary syndrome

Dulmage, Brittany; Geskin, Larisa J.; Guitart, Joan; Akilov, Oleg E.

doi:10.1111/exd.13261

Cited by 30 publications

(32 citation statements)

References 110 publications

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“…TOX (thymus high-mobility group box) is considered a marker of malignant lymphocytes in CTCL tumors (9,22,23). Strikingly, clustering of the TOX þ cells from each tumor sample (Supplementary Fig.…”

Section: Translational Relevancementioning

confidence: 99%

Single-Cell Lymphocyte Heterogeneity in Advanced Cutaneous T-cell Lymphoma Skin Tumors

Gaydosik

Tabib

Geskin

et al. 2019

Clinical Cancer Research

103

130

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Purpose: The heterogeneity of tumor cells presents a major challenge to cancer diagnosis and therapy. Cutaneous T-cell lymphomas (CTCL) are a group of T lymphocyte malignancies that primarily affect skin. Lack of highly specific markers for malignant lymphocytes prevents early diagnosis, while only limited treatment options are available for patients with advanced stage CTCL. Droplet-based single-cell transcriptome analysis of CTCL skin biopsies opens avenues for dissecting patient-specific T lymphocyte heterogeneity, providing a basis for identifying specific markers for diagnosis and cure of CTCL. Experimental Design: Single-cell RNA-sequencing was performed by Droplet-based sequencing (10X Genomics), focusing on 14,056 CD3 þ lymphocytes (448 cells from normal and 13,608 cells from CTCL skin samples) from skin biopsies of 5 patients with advanced-stage CTCL and 4 healthy donors. Protein expression of identified genes was validated in advanced stage CTCL skin tumors by immunohistochemistry and confocal immunofluorescence microscopy. Results: Our analysis revealed a large inter-and intratumor gene expression heterogeneity in the T lymphocyte subset, as well as a common gene expression signature in highly proliferating lymphocytes that was validated in multiple advanced-stage skin tumors. In addition, we established the immunologic state of reactive lymphocytes and found heterogeneity in effector and exhaustion programs across patient samples. Conclusions: Single-cell analysis of CTCL skin tumor samples reveals patient-specific landscapes of malignant and reactive lymphocytes within the local microenvironment of each tumor, giving an unprecedented view of lymphocyte heterogeneity and identifying tumor-specific molecular signatures, with important implications for diagnosis and personalized disease treatment.

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Section: Translational Relevancementioning

confidence: 99%

Single-Cell Lymphocyte Heterogeneity in Advanced Cutaneous T-cell Lymphoma Skin Tumors

Gaydosik

Tabib

Geskin

et al. 2019

Clinical Cancer Research

103

130

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“…It is crucial to identify individuals with high risk of progression. 76 Traditionally, overall clinical characteristics, such as skinstage (T) or histologic features for example large cell transformation (LCT), identify patients with poor prognosis. It is worth emphasizing that there is great heterogeneity in these subclasses of PCL.…”

Section: Nlr and Lmr In T And Nk-cell Lymphomas Primary Cutaneous T-cmentioning

confidence: 99%

“…Elevated absolute lymphocyte count and eosinophilia are associated with disease progression and disease-specific death. 76 Changes in the T-cell population can also be correlated with the risk of disease progression. In Abeni et al 78 study, the number of CD8+ T cells below 600/mL has been associated with a worse prognosis in MF patients.…”

Section: Nlr and Lmr In T And Nk-cell Lymphomas Primary Cutaneous T-cmentioning

confidence: 99%

<p>The Neutrophil to Lymphocyte and Lymphocyte to Monocyte Ratios as New Prognostic Factors in Hematological Malignancies – A Narrative Review</p>

Stefaniuk¹,

Szymczyk²,

Podhorecka³

2020

CMAR

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Despite the presence of many hematological prognostic indexes, clinical course and overall survival are often highly variable even within the same patient subgroup. Recent studies suggest that simple, cost-effective, low-risk tests such as neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) may be used to evaluate the prognosis. Their role has been well confirmed in diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL) and multiple myeloma (MM), but until now the prognostic significance of NLR and LMR in leukemias has not been widely reported. In this article, we analyze the literature data on prognostic value of NLR and LMR in haematological malignancies in the context of classic prognostic factors and clinical course.

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“…During the past decade, several markers with variable efficiency for MF/SS diagnosis, outcome prediction, blood response to treatment or as potential therapeutic targets have been identified . Such markers are essential for sharing and publishing consistent data about diagnosis, staging, prognosis and response to therapies.…”

mentioning

confidence: 99%

Revisiting the initial diagnosis and blood staging of mycosis fungoides and Sézary syndrome with the KIR 3 DL 2 marker

et al. 2019

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Summary Background The early diagnosis of Sézary syndrome (SS) is challenging. Loss of CD7 and CD26 expression on CD4+ T cells is the currently used criterion in the initial diagnosis and staging of patients with SS. Objectives Our aim was to evaluate the respective value of CD26, CD7 and KIR3DL2 expression on CD4+ T cells and total lymphocytes at initial diagnosis of SS. Methods This prospective study included 254 patients with clinical features consistent with cutaneous T‐cell lymphoma seen at our institution between March 2014 and February 2019. Peripheral blood analysis by flow cytometry was performed for each patient at the time of diagnosis and during follow‐up. The diagnosis of SS was based on ISCL/EORTC criteria. Results The presence of KIR3DL2+ Sézary cells (SCs) ≥ 200 μL−1 correlated with the diagnosis of SS, with sensitivity of 88·6% and specificity of 96·3%. All 154 patients with either inflammatory skin disease or other haematological disease had KIR3DL2+ cells < 200 μL−1, while eight of them had CD4+ CD26− T cells ≥ 1000 μL−1. Of five patients with SS and lymphopenia, four had CD4+ CD7− T cells < 1000 μL−1 and three had CD4+ CD26− T cells < 1000 μL−1. However, all of them had KIR3DL2+ CD4+ T cells ≥ 200 μL−1. Among patients with available samples during evolution, all B1‐staged patients with ≥ 200 μL−1 KIR3DL2+ SCs at diagnosis evolved to B2 stage within 7 months. Conclusions KIR3DL2 expression on T cells is highly specific and helps the early diagnosis of SS, especially in those patients with lymphopenia. What's already known about this topic? In the ISCL/EORTC cutaneous T‐cell lymphoma (CTCL) categorization of blood involvement (B0–B2), B2 is defined as a T‐cell receptor clonal rearrangement in blood, associated with high blood‐smear Sézary cell (SC) count. Flow cytometry was developed to circumvent interobserver variability of SC manual counts; however, it mostly relies on detection of cells lacking CD7 and/or CD26 expression. We previously reported the reliability of KIR3DL2 as the first positive SC marker. What does this study add? Based on our analysis of 254 patients, we propose that KIR3DL2 be added to the ISCL/EORTC criteria for initial diagnosis of Sézary syndrome (SS) and B2 staging. This marker improved sensitivity of SS B2‐stage CTCL diagnosis with a specificity > 95%, especially for patients with lymphopenia. We found KIR3DL2 helped early diagnosis of SS and was more reliable than CD26 in assessing blood tumour burden during therapy. What is the translational message? SC quantification is the major means of staging at initial diagnosis and monitoring blood tumour burden in a clinical trials setting. We recommend using a threshold value of KIR3DL2+ SCs ≥ 200 μL−1 or KIR3DL2+ SCs/lymphocytes ≥ 10% in the diagnostic criteria of SS and propose a novel algorithm for CTCL B2 blood staging.

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The biomarker landscape in mycosis fungoides and Sézary syndrome

Cited by 30 publications

References 110 publications

Single-Cell Lymphocyte Heterogeneity in Advanced Cutaneous T-cell Lymphoma Skin Tumors

Single-Cell Lymphocyte Heterogeneity in Advanced Cutaneous T-cell Lymphoma Skin Tumors

<p>The Neutrophil to Lymphocyte and Lymphocyte to Monocyte Ratios as New Prognostic Factors in Hematological Malignancies – A Narrative Review</p>

Revisiting the initial diagnosis and blood staging of mycosis fungoides and Sézary syndrome with the KIR 3 DL 2 marker

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