Contribution of STAT3 and RAD23B in primary S ézary cells to histone deacetylase inhibitor FK228 resistance

This study investigates RAD23B and STAT3 gene perturbations in a large cohort of primary Sézary cells and the effect of FK228 treatment on tyrosine phosphorylation of STAT3 (pYSTAT3) and RAD23B expression. We report RAD23B copy number variation in 10% (12/119; p ≤ 0.01) of S S patients, associated with reduced mRNA expression (p = 0.04).
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Original Article Source Type: research

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Abstract Mogamulizumab, approved by the FDA for relapsed or refractory mycosis fungoides and Sézary syndrome, improves progression-free survival compared to vorinostat in the largest trial to date in cutaneous T-cell lymphoma, with particular efficacy in leukemic disease, but carries a risk of immune-mediated toxicities with concomitant depletion of regulatory T-cells. PMID: 31615932 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Authors: Ying Z, Shiue L, Park K, Kollet J, Bijani P, Goswami M, Duvic M, Ni X Abstract [This corrects the article DOI: 10.18632/oncotarget.26900.]. PMID: 31534633 [PubMed - in process]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Mycosis fungoides (MF) and Sezary syndrome (SS) are subtypes of extranodal T cell nonHodgkin lymphoma, and are the most common forms of cutaneous T cell lymphoma (CTCL). Although both subtypes involve the skin, SS is characterized by leukemic involvement of malignant T cells that typically match the clone found in the skin. MF has a plethora of clinicopathological variants, one of which is the pigmented purpuric dermatosis (PPD)-like MF. Although the PPD-like MF is rarely reported, it has been previously described as either preceding MF or appearing as the initial presentation of MF.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
This study functionally interrogated 9 PLCG1 mutations (p.R48W, p.S312L, p.D342N, p.S345F, p.S520F, p.R1158H, p.E1163K, p.D1165H and the in-frame indel p.VYEEDM1161V) identified in S ézary Syndrome, the leukemic variant of CTCL. The mutations were demonstrated in diagnostic samples and persisted in multiple tumor compartments over time, except in patients who achieved a complete clinical remission. In basal conditions, the majority of the mutations confer PLCγ1 gain-of-functio n activity through increased inositol phosphate production and downstream activation of NFκB, AP-1 and NFAT transcriptional activity.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Original Article Source Type: research
Aseem K Tiwari, Dinesh Arora, Pratibha Dhiman, Sheilly Kapoor, Geet Aggarwal, Ravi C Dara, Ashok VaidAsian Journal of Transfusion Science 2019 13(1):66-69Sezary syndrome (SS) is more aggressive leukemic variant of cutaneous T-cell lymphoma in which a significant number of circulating malignant (Sezary) cells are observed in peripheral blood. Although single-agent or combination chemotherapy regimens have produced moderately high response rates in patients with advanced-stage SS, these responses are invariably not durable. Extracorporeal photopheresis (ECP) is recommended as an immunomodulator treatment, offering better lif...
Source: Asian Journal of Transfusion Science - Category: Hematology Authors: Source Type: research
Publication date: Available online 6 June 2019Source: Best Practice &Research Clinical HaematologyAuthor(s): Xochiquetzal U. Martinez, Cosimo Di Raimondo, Farah R. Abdulla, Jasmine Zain, Steven T. Rosen, Christiane QuerfeldAbstractMycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of cutaneous lymphoma, accounting for approximately 60% of cutaneous T-cell lymphomas. Diagnosis requires correlation of clinical, histologic, and molecular features. A multitude of factors have been linked to the aetiopathogenesis, however, none have been definitively proven. Erythrodermic MF (E-MF) and SS share...
Source: Best Practice and Research Clinical Haematology - Category: Hematology Source Type: research
We examined the linkage between these mutations and autoimmune symptoms and disorders, in cases of obvious and suspected LGL leukemia. We then summarized and compared mutations in a set of other rare leukemias that also have JAK/STAT signaling pathway activation brought about by genomic changes. These include T-cell acute lymphoblastic leukemia (T-ALL), T-cell prolymphocytic leukemia (T-PLL), cutaneous T-cell lymphoma (CTCL), select peripheral T-cell lymphoma (PTCL), and adult T-cell leukemia/lymphoma (ATLL). Though STAT3 activation is common in these leukemias, the way in which it is achieved, such as the activating cytok...
Source: Best Practice and Research Clinical Haematology - Category: Hematology Source Type: research
This study was to explore the molecular mechanisms underlying clinical response versus non-response in patients with L-CTCL. We performed blood transcriptional profiling of ten L-CTCL patients at Day 2 and 1 month post- ECP compared to pre-ECP baseline using Agilent Whole Human Genome Microarray technology. Differentially expressed genes (DEGs) between five clinically-responsive patients and five clinically-resistant patients were cross-compared. Higher numbers of genes were modulated in responders than non-responders after ECP at both Day 2 and 1 month, with two thirds of DEGs down-regulated. The down-regulated DEGs at 1 ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
CONCLUSIONS: Our results show that STAT3 is activated in advanced cases and associated with large-cell transformation, while the activation of NFAT and NFκB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. This article is protected by copyright. All rights reserved. PMID: 31049933 [PubMed - as supplied by publisher]
Source: The British Journal of Dermatology - Category: Dermatology Authors: Tags: Br J Dermatol Source Type: research
In conclusion, we believe that the data presented in this research add new relevant information for a better definition of the pathological states associated with HTLV-1 infection, particularly in relation to the distinct subcellular expression of HBZ in the different pathological contests and related pathologies. Whether HBZ cytoplasmic and nuclear localization in the natural history of HTLV-1 infection represents a marker of infection or is part of the mechanism governing the evolution toward HAM/TSP or ATL is the challenge for future investigation. Author Contributions GF, MB, and RA conceived the work. GF, MB, and AT...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
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