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Blood Dec 2021
Topics: Gene Expression Profiling; Humans; Sezary Syndrome; Skin Neoplasms
PubMed: 34914833
DOI: 10.1182/blood.2021013433 -
International Journal of Molecular... Mar 2022Epigenetic modifications rarely occur in isolation (as single "epigenetic modifications"). They usually appear together and form a network to control the epigenetic... (Review)
Review
Epigenetic modifications rarely occur in isolation (as single "epigenetic modifications"). They usually appear together and form a network to control the epigenetic system. Cutaneous malignancies are usually affected by epigenetic changes. However, there is limited knowledge regarding the epigenetic changes associated with cutaneous lymphomas. In this review, we focused on cutaneous T-cell lymphomas such as mycosis fungoides, Sézary syndrome, and anaplastic large cell lymphoma. With regard to epigenetic changes, we summarize the detailed chemical modifications categorized into DNA methylation and histone acetylation and methylation. We also summarize the epigenetic modifications and characteristics of the drug for cutaneous T-cell lymphoma (CTCL). Furthermore, we discuss current research on epigenetic-targeted therapy against cutaneous T-cell lymphomas. Although the current method of treatment with histone deacetylase inhibitors does not exhibit sufficient therapeutic benefits in all cases of CTCL, epigenetic-targeted combination therapy might overcome this limitation for patients with CTCL.
Topics: Epigenesis, Genetic; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms
PubMed: 35408897
DOI: 10.3390/ijms23073538 -
Blood Advances Sep 2023The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains unclear. Using single-cell RNA or T-cell receptor (TCR) sequencing of 32 619 CD3+CD4+ and CD26+/CD7+ and...
The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains unclear. Using single-cell RNA or T-cell receptor (TCR) sequencing of 32 619 CD3+CD4+ and CD26+/CD7+ and 29 932 CD3+CD4+ and CD26-/CD7- lymphocytes from the peripheral blood of 7 patients with CTCL, coupled to single-cell ATAC-sequencing of 26,411 CD3+CD4+ and CD26+/CD7+ and 33 841 CD3+CD4+ and CD26-/CD7- lymphocytes, we show that tumor cells in Sézary syndrome and mycosis fungoides (MF) exhibit different phenotypes and trajectories of differentiation. When compared to MF, Sézary cells exhibit narrower repertoires of TCRs and exhibit clonal enrichment. Surprisingly, we identified ≥200 mutations in hematopoietic stem cells from multiple patients with Sézary syndrome. Mutations in key oncogenes were also present in peripheral Sézary cells, which also showed the hallmarks of recent thymic egression. Together our data suggest that CTCL arises from mutated lymphocyte progenitors that acquire TCRs in the thymus, which complete their malignant transformation in the periphery.
Topics: Humans; Sezary Syndrome; Dipeptidyl Peptidase 4; Skin Neoplasms; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Receptors, Antigen, T-Cell
PubMed: 37531660
DOI: 10.1182/bloodadvances.2022008562 -
Cancers Jan 2023Mycosis fungoides and Sézary syndrome are epidermotropic cutaneous lymphomas, and both of them are rare diseases. Mycosis fungoides is the most frequent primary... (Review)
Review
Mycosis fungoides and Sézary syndrome are epidermotropic cutaneous lymphomas, and both of them are rare diseases. Mycosis fungoides is the most frequent primary cutaneous lymphoma. In about 25% of patients with mycosis fungoides, the disease may progress to higher stages. The pathogenesis and risk factors of progression in mycosis fungoides and Sézary syndrome are not yet fully understood. Previous works have investigated inter- and intrapatient tumor cell heterogeneity. Here, we overview the role of the tumor microenvironment of mycosis fungoides and Sézary syndrome by describing its key components and functions. Emphasis is put on the role of the microenvironment in promoting tumor growth or antitumor immune response, as well as possible therapeutic targets. We focus on recent advances in the field and point out treatment-related alterations of the microenvironment. Deciphering the tumor microenvironment may help to develop strategies that lead to long-term disease control and cure.
PubMed: 36765704
DOI: 10.3390/cancers15030746 -
Archives of Dermatological Research Nov 2023Treating atopic dermatitis (AD) with dupilumab, a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), may be associated with the...
Treating atopic dermatitis (AD) with dupilumab, a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), may be associated with the progression of mycosis fungoides (MF).This study aims to examine the associations between the length of dupilumab treatment, age and sex, and the onset of MF.An institutional data registry and literature search were used for a retrospective cross-sectional study. Only patients with a diagnosis of MF on dupilumab for the treatment of AD and eczematous dermatitis were included.The primary outcome was the length of dupilumab exposure, age, sex, and the onset of MF. Linear correlations (Pearson) and Cox regression analysis were used to assess the correlation and the risk.A total of 25 patients were included in this study. Five eligible patients were identified at our institution. In addition, a PubMed review identified an additional 20 patients. At the time of MF diagnosis, the median age was 58, with 42% female. Disease history was significant for adult-onset AD in most patients (n = 17, 65.4%) or recent flare of AD previously in remission (n = 3, 11.5%). All patients were diagnosed with MF, and one patient progressed to Sézary syndrome while on dupilumab, with an average duration of 13.5 months of therapy prior to diagnosis. Tumor stage at diagnosis of MF was described in 19 of the cases and ranged from an early-stage disease (IA) to advanced disease (IV). Treatment strategies included narrow-band UVB therapy, topical corticosteroids, brentuximab, pralatrexate, and acitretin. Male gender, advanced-stage disease, and older age correlated significantly with the hazard of MF onset and a shorter time to onset during dupilumab treatment.Our results suggest a correlation between the duration of dupilumab treatment and the diagnosis of MF, the higher MF stage at diagnosis, and the shorter the duration of using dupilumab to MF onset. Furthermore, elderly male patients appeared to be more at risk as both male gender and older age correlated with a hazard of MF diagnosis. The results raise the question as to whether the patients had MF misdiagnosed as AD that was unmasked by dupilumab or if MF truly is an adverse effect of treatment with dupilumab. Close monitoring of these patients and further investigation of the relationship between dupilumab and MF can shed more light on this question .
Topics: Adult; Humans; Male; Female; Aged; Middle Aged; Cross-Sectional Studies; Retrospective Studies; Mycosis Fungoides; Dermatitis, Atopic; Antibodies, Monoclonal; Skin Neoplasms
PubMed: 37270763
DOI: 10.1007/s00403-023-02652-z -
Hematology/oncology Clinics of North... Aug 2019Non-Hodgkin's lymphoma (NHL) encompasses a diverse collection of systemic and primary cutaneous lymphomas. Cutaneous T-cell lymphomas (CTCLs) represent about 13% of all... (Review)
Review
Non-Hodgkin's lymphoma (NHL) encompasses a diverse collection of systemic and primary cutaneous lymphomas. Cutaneous T-cell lymphomas (CTCLs) represent about 13% of all NHLs, which are further subdivided into a heterogeneous group with vastly different presentations and histologic features. Diagnosis requires integration of clinical, pathologic, and molecular features. Among CTCLs, mycosis fungoides and Sézary syndrome are the most prevalent. Treatment is aimed at limiting morbidity and halting disease progression. Hematopoietic stem cell transplantation is the only therapy with curative intent.
Topics: Antineoplastic Agents; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Progression-Free Survival; Sezary Syndrome; Skin Neoplasms
PubMed: 31229162
DOI: 10.1016/j.hoc.2019.04.004 -
Cytometry. Part B, Clinical Cytometry Mar 2021
Topics: Antigens, CD; Flow Cytometry; Humans; Immunophenotyping; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes
PubMed: 32083391
DOI: 10.1002/cyto.b.21872 -
Cytometry. Part B, Clinical Cytometry Mar 2021This review discusses the definition and major categories of cutaneous T-cell lymphoma, Sézary syndrome and mycosis fungoides, and the role of immunophenotyping in... (Review)
Review
This review discusses the definition and major categories of cutaneous T-cell lymphoma, Sézary syndrome and mycosis fungoides, and the role of immunophenotyping in their diagnosis. The following key points are raised: (a) Sézary syndrome and mycosis fungoides cells most often have a characteristic CD3+ CD4+ CD7- and/or CD26- immunophenotype. (b) This immunophenotype is not specific, but can assist in the distinction from non-neoplastic T cells and other subtypes of mature T-cell neoplasm. (c) However, small subsets of normal and reactive T-cells can have an overlapping immunophenotype, and can be distinguished by evaluating for additional changes in antigen expression.
Topics: Antigens, CD; Flow Cytometry; Humans; Immunophenotyping; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes
PubMed: 32516521
DOI: 10.1002/cyto.b.21888 -
Cytometry. Part B, Clinical Cytometry Mar 2021Flow cytometry of peripheral blood has become the standard tool for the diagnosis and monitoring of Sézary syndrome. However, there is a sense of frustration among... (Review)
Review
Flow cytometry of peripheral blood has become the standard tool for the diagnosis and monitoring of Sézary syndrome. However, there is a sense of frustration among dermatologists and oncologist regarding the challenges in interpreting vague flow cytometry (FC) reports, which often include an array of numbers and percentages that are difficult to interpret and fail to elucidate quantitatively or qualitatively the presence or absence of an abnormal T cell population. From the clinicians' perspective, a report of the flow cytometric evaluation for Sézary syndrome should include the following items: presence or absence of abnormal T-cells, phenotype of abnormal cells, and quantity of abnormal cells to disease burden and for staging.
Topics: Flow Cytometry; Humans; Immunophenotyping; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes
PubMed: 32017375
DOI: 10.1002/cyto.b.21870 -
The Australasian Journal of Dermatology Feb 2021Primary cutaneous lymphomas represent a heterogeneous group of T- and B-cell lymphomas with distinct clinical presentations, histopathologic features, treatment... (Review)
Review
Primary cutaneous lymphomas represent a heterogeneous group of T- and B-cell lymphomas with distinct clinical presentations, histopathologic features, treatment approaches and outcomes. The cutaneous T-cell lymphomas, which include mycosis fungoides and Sézary syndrome, account for the majority of the cutaneous lymphomas. This Clinical Practice Statement is reflective of the current clinical practice in Australia. An expanded form of the Clinical Practice Statement (and updates), along with helpful patient resources and access to support groups, can be found at the following (http://www.australasianlymphomaalliance.org.au).
Topics: Biopsy; Hematologic Tests; Humans; Mycosis Fungoides; Neoplasm Staging; Prognosis; Sezary Syndrome; Skin; Skin Neoplasms; Survival Rate
PubMed: 33368169
DOI: 10.1111/ajd.13467