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Cutaneous Lymphoma
Published in Debjani Sahni, Adam Lerner, Bilal Fawaz, Advanced Skin Cancer, 2022
PC-DLBCL, leg-type occurs almost exclusively in elderly women.1 As the name implies, this lymphoma arises most commonly on the distal legs. However, the same designation still applies in 20% of cases involving other body sites, most notably the upper extremities and trunk.1 H&E findings are similar to other forms of CBCL, but IHC staining is positive for Bcl-2, MUM-1, FOX-P1, and MYC. Bcl-6 staining is variable and not helpful in establishing the diagnosis.1 In contrast to the first two CBCLs, extracutaneous disease is common, and prognosis is less favorable, with a disease-specific 5-year survival of only 40%–50%.1 Systemic chemotherapy with R-CHOP is often recommended, with or without adjuvant radiotherapy.1
Nucleic Acid-Based, mRNA-Targeted Therapeutics for Hematologic Malignancies
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
To target the malignant B-cell lymphomas, we are investigating the utility of targeting Bcl6 mRNA. Bcl6 is a zinc finger protein, which acts as a sequence-specific transcriptional repressor (111). Although Bcl6 mRNA is ubiquitous, its expression is highest in germinal center B-cells where it is thought to repress the expression of genes involved in B-cell activation, cell cycle progression, and terminal differentiation. In non-Hodgkin’s lymphomas, Bcl6 is the most frequently deregulated gene, and abnormal expression is found in approximately 30% to 40% of DLCL, and approximately 14% of follicular lymphomas (FL). We found that cells transfected with an appropriately targeted ASODN exhibited an approximately 50% drop in viability within 24 hours. Coincident with the drop in viability, we found a sevenfold decrease in Bcl6 mRNA expression in cells transfected with 1310, and little change in cells transfected with control oligonucleotides (Fig. 2).
Diffuse Large B-Cell Lymphoma and its Variants
Published in Wojciech Gorczyca, Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
The biological consequences of BCL6 expression in DLBCL might vary according to the presence or absence and the nature of the underlying alteration of the BCL6 gene [56]. Genes that correlate most with the outcome in the DLBCL include nor1, pde4b, pkc-β2 [4], LMO2, BCL6, FN1, CCND2, SCYA3, and BCL2 [10]. The expression of LMO2, FN1, and BCL6 correlated with prolonged survival, and the expression of CCND2, SCYA3, and BCL2 correlated with short survival [10].
Pembrolizumab in the treatment of refractory primary mediastinal large B-cell lymphoma: safety and efficacy
Published in Expert Review of Anticancer Therapy, 2021
Vincent Camus, Camille Bigenwald, Vincent Ribrag, Julien Lazarovici, Fabrice Jardin, Clémentine Sarkozy
PMBL tumor cells are thought to derive from thymic B cells. Thymic B cells reside at the cortico-medullary junction of the thymus and represent about 1% of total thymic cells [28]. They are mostly naïve B cells and are distinct from peripheral blood B cells [29]. Moreover, they seem to present a phenotype close to antigen-presenting cells with an overexpression of MHC II and CD86. In addition, they highly express Aire, whereas peripheral B cells do not express Aire. These data do not support the hypothesis of a peripheral B cells-homing [30] to the thymus. However, evaluation of thymic B cells remains scarce in the literature. Of note, in PMBL, the high level of BCL6 expression, as well as the high mutation burden, contrasts with the hypothesis of a naïve B cell-of-origin. However, the spectrum of mutations observed in BCL6 was not found in GC B-cell lymphoma (FL and DLBCL), suggesting a distinct COO [31].
Therapeutic melanoma vaccine with cancer stem cell phenotype represses exhaustion and maintains antigen-specific T cell stemness by up-regulating BCL6
Published in OncoImmunology, 2020
Patrycja Czerwinska, Marcin Rucinski, Nikola Wlodarczyk, Anna Jaworska, Iga Grzadzielewska, Katarzyna Gryska, Lukasz Galus, Jacek Mackiewicz, Andrzej Mackiewicz
Microarray technology enabled the identification of a BCL6 transcriptional repressor as a gene that is significantly differentially expressed in all of the tested groups. The role of Bcl6 in T cell differentiation, survival, and long-term proliferation has been studied extensively.11-16 Bcl6 enforced the progenitor fate of antigen-specific T cells and facilitated their longevity and proliferation. Moreover, Bcl6 repressed exhaustion of antigen-specific T cells, which correlated with down-regulation of “exhaustion markers”.14 Also, the expression of BCL6 is tightly regulated during the development of specific T cell subpopulations and its expression is induced and modulated by several cytokines (e.g., IFN-γ, IL-6, type I IFN, IL-12, TGF-β, and TNF-α) in a variety of cell types17-23 and repressed by IL2-STAT5 signaling.24
Clinicopathologic significance and therapeutic implication of de novo CD5+ diffuse large B-cell lymphoma
Published in Hematology, 2019
Huifen Tang, Hui Zhou, Juying Wei, Hui Liu, Wenbin Qian, Xiaohui Chen
Pathological features of CD5+ vs. CD5– DLBCL patients were characterized by comparing their protein expression profiles (Table 2). CD10 was positive in 1 (3.3%) of the 30 patients with CD5+ DLBCL and in 25 (43.1%) of the 109 patients with CD5− DLBCL. The CD10 positive rate was significantly lower in the CD5+ DLBCL group than that in the CD5− DLBCL group (P < 0.0001). BCL-2 was positive in 89.3% of the patients with CD5+ DLBCL and in 55.4% of the patients with CD5− DLBCL, showing a significant difference (P = 0.001). BCL-6 was positive in 62.1% of the patients with CD5+ DLBCL and in 80.7% of the patients with CD5− DLBCL, showing that BCL6 positive rate was significantly lower in the CD5+ DLBCL group than that in the CD5− DLBCL group (P = 0.043). The MUM-1 was positive in 82.1% of the patients with CD5+ DLBCL and in 77.9% of the patients with CD5− DLBCL (No significance). Similarly, there was no significant difference in the expression of EBER in CD5+ DLBCL and CD5− DLBCL. However, Chuang WY et al. [20] have collected 174 DLBCL cases in Taiwan and performed immunophenotyping and detection of Epstein–Barr virus (EBV)-encoded RNA (EBER) by in situ hybridization. They indicated that EBER positivity was associated with IPI > 2, stage III–IV, and B symptoms which was not an independent adverse prognostic factor, but its effect was likely to be due to accompanying adverse clinical parameters.