Molecular pathogenesis of Cutaneous T cell Lymphoma: Role of chemokines, cytokines, and dysregulated signaling pathways

Patil, Kalyani; Kuttikrishnan, Shilpa; Khan, Abdul Quaiyoom; Faried, Ahmad; Alam, Majid; Buddenkotte, Joerg; Ahmad, Aamir; Steinhoff, Martin; Uddin, Shahab

doi:10.1016/j.semcancer.2021.12.003

Cited by 33 publications

(31 citation statements)

References 244 publications

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“…For instance, as previously established, drug eruptions are known to morphologically resemble a wide range of skin conditions, both clinically and histopathologically. Likewise, CTCLs are known to exhibit a wide spectrum of clinical, immunological and genetic phenotypes ( 32 ), thereby accounting for the observed variation in cytokine/chemokine profiles. Ultimately, although not all disease types could be distinguished using the chosen analyte panel, these results suggest the potential to refine inflammatory signatures pertaining to disease type, eventually leading to diagnostic differentiation by inflammatory markers.…”

Section: Discussionmentioning

confidence: 99%

Cytokine/Chemokine assessment as a complementary diagnostic tool for inflammatory skin diseases

et al. 2022

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Inflammatory skin conditions are the 4th leading cause of non-fatal health burden in the general population worldwide. The diagnosis of skin lesions due to systemic drug reactions, viral or bacterial exanthems, or in patients with psoriasis, atopic dermatitis or contact dermatitis is often difficult and relies heavily upon conventional histopathologic examination. Conversely, it is widely accepted that the cutaneous profile of inflammatory markers, or ‘inflammatory signature’, is differentially expressed in various skin conditions. In this pilot study, we investigated the possibility of inflammatory skin disease diagnosis from an immunological perspective in small punch biopsies. We collected lesional and perilesional punch biopsies from 139 patients suffering from a variety of inflammatory skin conditions and attending the Dermatology Department at the Princess Alexandra Hospital in Brisbane, Australia. Using bead-based immunoassays we were able to measure 13 out of 17 inflammatory markers from a pre-selected multi-analyte panel and to detect significant differences between lesional and perilesional biopsies from each individual patient. Hierarchical and unbiased clustering methods based on inflammatory signatures grouped psoriasis and atopic dermatitis lesions into individual clusters in contrast to other skin conditions, highlighting the potential of inflammatory signatures to be used as diagnostic differentiators and to inform alternative targets in anti-inflammatory treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Cytokine/Chemokine assessment as a complementary diagnostic tool for inflammatory skin diseases

et al. 2022

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Section: Staging Molecular Biology and Prognosismentioning

confidence: 99%

“…Therefore, forming a clonal population of T cells with specific genetic-molecular alterations results in precarious equilibrium with the cellular and humoral part of the microenvironment. 11 In 2007 staging system was revised by the International Society for Cutaneous Lymphomas (ISCL) and the EORTC to incorporate advances related to tumor cell biology and diagnostic techniques, including the status of blood involvement. Investigators at the National Cancer Institute retrospectively analyzed 152 patients who underwent uniform pathologic staging.…”

Section: Introductionmentioning

confidence: 99%

The Treatment of Advanced-Stage Mycosis Fungoides and Sezary Syndrome: A Hematologist's Point of View.

Giordano

Pagano

2022

Mediterr J Hematol Infect Dis

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Cutaneous T-cell lymphomas are a heterogenous group of T-cell neoplasms involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS). Mycosis fungoides (MF) is usually associated with an indolent clinical course and intermittent, stable, or slow progression of the lesions. Extracutaneous involvement (lymph nodes, blood, or less commonly other organs) or large cell transformation (LCT) may be seen in advanced-stage disease. Sezary syndrome (SS) is a rare leukemic subtype of CTCL characterized by significant blood involvement, erythroderma, and often lymphadenopathy. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as vorinostat, brentuximab vedotin, and mogamulizumab. This review aims to discuss the diagnosis and management of advanced-stages MF and SS.

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“…Cutaneous T-cell lymphoma (CTCL) defines a variety of neoplasms characterized by the accumulation of mature T-cells in the skin, and includes ATLL cases with cutaneous homing [reviewed by ( 73 )]. An analysis of a panel of CTCL cell lines and primary CTCL samples (including ATLL lymph node biopsies) revealed significant downregulation of miR-150 in CTCL cells compared to normal CD4+ T-cells ( 74 ).…”

Section: Htlv-1 and The Cellular Mirna Network In Infected T-cells An...mentioning

confidence: 99%

MiR-150 in HTLV-1 infection and T-cell transformation

et al. 2022

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Human T-cell leukemia virus-1 (HTLV-1) is a retrovirus that persistently infects CD4+ T-cells, and is the causative agent of adult T-cell leukemia/lymphoma (ATLL), tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) and several inflammatory diseases. T-cell transformation by HTLV-1 is driven by multiple interactions between viral regulatory proteins and host cell pathways that govern cell proliferation and survival. Studies performed over the last decade have revealed alterations in the expression of many microRNAs in HTLV-1-infected cells and ATLL cells, and have identified several microRNA targets with roles in the viral life cycle and host cell turnover. This review centers on miR-150-5p, a microRNA whose expression is temporally regulated during lymphocyte development and altered in several hematological malignancies. The levels of miR-150-5p are reduced in many HTLV-1-transformed- and ATLL-derived cell lines. Experiments in these cell lines showed that downregulation of miR-150-5p results in activation of the transcription factor STAT1, which is a direct target of the miRNA. However, data on miR-150-5p levels in freshly isolated ATLL samples are suggestive of its upregulation compared to controls. These apparently puzzling findings highlight the need for more in-depth studies of the role of miR-150-5p in HTLV-1 infection and pathogenesis based on knowledge of miR-150-5p-target mRNA interactions and mechanisms regulating its function in normal leukocytes and hematologic neoplasms.

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Molecular pathogenesis of Cutaneous T cell Lymphoma: Role of chemokines, cytokines, and dysregulated signaling pathways

Cited by 33 publications

References 244 publications

Cytokine/Chemokine assessment as a complementary diagnostic tool for inflammatory skin diseases

Cytokine/Chemokine assessment as a complementary diagnostic tool for inflammatory skin diseases

The Treatment of Advanced-Stage Mycosis Fungoides and Sezary Syndrome: A Hematologist's Point of View.

MiR-150 in HTLV-1 infection and T-cell transformation

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