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Background: Recent genomic studies revealed enhancer of zeste homolog 2 (EZH2) gain‐of‐function mutations, representing novel therapeutic targets in follicular lymphoma (FL) in around one quarter of patients. However, these analyses relied on single‐site tissue biopsies and did not investigate the spatial heterogeneity and temporal dynamics of these alterations. Objectives: We aimed to perform a systematic analysis of EZH2 mutations using paired tissue (tumor biopsies [TB]) and liquid biopsies (LB) collected prior to treatment within the framework of a nationwide multicentric study. Methods: Pretreatment LB and TB samples were collected from 123 patients. Among these, 114 had paired TB and LB, with 39 patients characterized with paired diagnostic and relapse samples available. The EZH2 mutation status and allele burden were assessed using an in‐house‐designed, highly sensitive multiplex droplet digital PCR assay. Results: EZH2 mutation frequency was found to be 41.5% in the entire cohort. In patients with paired TB and LB samples, EZH2 mutations were identified in 37.8% of the patients with mutations exclusively found in 5.3% and 7.9% of TB and LB samples, respectively. EZH2 mutation status switch was documented in 35.9% of the patients with paired diagnostic and relapse samples. We also found that EZH2 wild‐type clones may infiltrate the bone marrow more frequently compared to the EZH2 mutant ones. Conclusion: The in‐depth spatio‐temporal analysis identified EZH2 mutations in a considerably higher proportion of patients than previously reported. This expands the subset of FL patients who most likely would benefit from EZH2 inhibitor therapy. [ABSTRACT FROM AUTHOR]

In the pathogenesis of chronic lymphocytic leukemia (CLL) the microenvironment plays an important role, as it produces survival signals and mediates drug resistance. Lenalidomide, which has immunomodulatory effect, can enhance the activation of T‐, NK‐cells and endothelial cells, however there are no data available whether it can modulate bone marrow stromal cells (BMSCs). In our study, we investigated the effects of lenalidomide on BMSCs and CLL cells. CLL cells were cultured alone or with BMSCs and were treated with lenalidomide. Apoptosis, immunophenotype, and cytokine secretion of BMSCs and CLL cells were determined by flow cytometry. Lenalidomide slightly increased the apoptosis of CLL cells and abrogated the anti‐apoptotic effect of BMSCs on CLL cells. Lenalidomide treatment decreased the expression of antigens on CLL cells, which mediate the interactions with the microenvironment. Interestingly, lenalidomide enhanced the expression of IRF4 and the co‐stimulatory molecule CD86. The secretion of several cytokines was not changed significantly by lenalidomide. CD49d‐negative CLL cases were more sensitive to lenalidomide treatment. Our results suggest that lenalidomide has a limited effect on BMSCs, but it renders CLL cells more immunogenic and unresponsive to survival signals provided by BMSCs. [ABSTRACT FROM AUTHOR]

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The pathogenesis of Dupuytren's disease is unclear, but inflammatory mechanisms might be supposed in the background. Materials and methods: The ratios of the subsets of monocytes and lymphocytes in the peripheral blood were measured according to the stage of the disease of 39 Dupuytren's patients. They were compared with those of 29 healthy, age-matched controls. The measurements were accomplished by flow-cytometry. Results: In an active stage, the patients had significantly increased ratios of monocytes, NK-like T-cells, whereas significantly decreased ratio of B-lymphocytes, including CD5+ B-cells. The ratios of CD4+, CD8+ T-cells and NK-cells did not change significantly. In the advanced stage, the ratios of monocytes and B-lymphocytes remained constant, but the ratios of T-cells decreased significantly. In four cases among Dupuytren's patients, mature B- or T-cell lymphoid malignancies occurred. Conclusions: Our results support the previous considerations that lymphocytes are involved in the pathogenesis of Dupuytren's disease and enhance the role of monocytes, NK-like T-cells and the alteration of immune response between the stages of the disease. [ABSTRACT FROM AUTHOR]

Uvod: Patogeneza Dupuytrenove bolesti je nejasna, no mogu se pretpostaviti upalni mehanizmi u njenoj pozadini. Materijali i metode: Mjerili smo udjele različitih podvrsta monocita i lim-focita u perifernoj krvi prema stadiju bolesti kod 39 bolesnika oboljelih od Dupuytrenove bolesti. Rezultate smo usporedili s rezultatima 29 zdravih kontrolnih ispitanika iz iste dobne skupine. Mjerenja su napravljena pomoću protočne citometrije. Rezultati: U aktivnom su stadiju bolesnici imali bitno povišen udio monocita, NK-stanica sličnih T-limfocitima, dok je udio B-limfocita bio značajno snižen, uključujući CD5+ B-limfocite. Udjeli CD4+, CD8+ T-limfocita i B-limfocita nisu se znatno promijenili. U naprednom su stadiju bolesti udjeli monocita i B-limfocita ostali konstantnima, no značajno su se snizili udjeli T-limfocita. U četiri slučaja među bolesnicima koji boluju od Dupuytrenove bolesti pojavile su se limfoidne neoplazme zrelih B- ili T-limfocita. Zaključci: Naši rezultati podupiru prijašnja mišljenja da su limfociti povezani s patogenezom Dupuytrenove bolesti te pojačavaju ulogu monocita, NK-stanica sličnih T-limfocitima i promjenu imunosnog odgovora između stadija bolesti. [ABSTRACT FROM AUTHOR]