Search

Agnieszka Karczmarczyk,1 Maciej Korpysz,2 Sylwia Bilska,3 Joanna Purkot,1 Marek Hus,3 Krzysztof Giannopoulos1,4 1Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland; 2Department of Biochemical Diagnostics, Medical University of Lublin, Lublin, Poland; 3Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland; 4Department of Hematology, St. John’s Cancer Centre, Lublin, PolandCorrespondence: Krzysztof Giannopoulos, Department of Experimental Hematooncology, Medical University of Lublin, Chodzki 1, Lublin, 20-093, Poland, Tel + 48 81448 6632, Fax + 48 81448 6634, Email krzysztof.giannopoulos@gmail.comPurpose: Among hematological malignancies, the expression profile of programmed cell death-1 (PD-1) and its ligands in multiple myeloma (MM) is still debated by numerous research groups. In current study, we characterized the expression of PD-1 and its ligands both on RNA and protein levels in MM patients. We have also attempted to analyze whether daratumumab therapy might overcome CD38-mediated immunosuppression that inhibits in particular CD8+ T-cell function.Patients and Methods: This study included 149 newly diagnosed MM patients and 15 relapsed/refractory MM patients before and after daratumumab treatment. The mRNA levels of PDCD1, PDCD1LG1, PDCD1LG2 and their splicing variants was assessed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Flow cytometry was used to characterize the surface expression of PD-1 and its ligands on plasma cells, B and T cells. The surface expression of PD-1 on T cells was assessed by flow cytometry before and after daratumumab treatment.Results: The mRNA expression of PDCD1LG1, PDCD1LG2 and their splicing variants were higher in plasma cells as compared to bone marrow mononuclear cells (BMMCs). Our results show that the percentage of plasma cells expressing PD-L1 was significantly higher than plasma cells expressing PD-L2 (p< 0.0001) in bone marrow (BM) of MM patients. There was no significant difference between the percentage of plasma cells expressing PD-1 and B cells expressing PD-1 in BM of MM patients (11.19% vs 8.91%). We also found that the percentage of CD8+PD-1+ T cells was significantly higher than CD4+PD-1+T cells in BM (p< 0.0001) of MM patients. Here, we observed no change in PD-1 expression on CD4+ and CD8+ T cells after the daratumumab treatment.Conclusion: The PD-1 and its ligands might represent an interesting target for MM immunotherapy, as one would target both malignant plasma cells as well as the immune cells that play a key role in tumor escape mechanisms.Keywords: PD-1, PD-L1, PD-L2, daratumumab, multiple myeloma

Marta Masternak,1 Bartosz Puła,2 Joanna Knap,1 Anna Waszczuk-Gajda,3 Joanna Drozd-Sokołowska,3 Kamil Wdowiak,4 Sebastian Grosicki,5 Izabela Kozłowska,6 Marta Kaźmierczak,6 Anna Łabędź,7 Łukasz Szukalski,8 Kamil Wiśniewski,2 Edyta Subocz,9 Janusz Hałka,10 Agnieszka Szymczyk,11 Marek Hus,12 Krzysztof Jamroziak,2 Krzysztof Giannopoulos13 1Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland; 2Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland; 3Department of Hematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland; 4Department of Internal Medicine and Oncological Chemotherapy, Silesian Medical University, Katowice, Poland; 5Department of Hematology and Cancer Prevention in Chorzow, Faculty of Health Sciences in Bytom, Silesian Medical University, Katowice, Poland; 6Department of Hematology and Cancer Prevention, Municipal Hospital in Chorzów, Chorzów, Poland; 7Department of Hematology, Rydrygier’s Hospital in Cracow, Cracow, Poland; 8Department of Hematology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Toruń, Poland; 9Department of Hematology, Military Institute of Medicine, Warsaw, Poland; Clinical Department of Hematology, Independent Public Healthcare Centre of the Ministry of Internal Affairs and Administration with Warmia-Mazury Region’s Oncology Centre in Olsztyn, Olsztyn, Poland; 10Clinical Department of Hematology, Independent Public Healthcare Centre of the Ministry of Internal Affairs and Administration with Warmia-Mazury Region’s Oncology Centre in Olsztyn, Olsztyn, Poland; 11Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland; Hematology Department, St John’s Cancer Center, Lublin, Poland; 12Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland; 13Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland; Hematology Department, St John’s Cancer Center, Lublin, PolandCorrespondence: Krzysztof Giannopoulos Tel +48 81448 6632Fax +48 81448 6634Email krzysztof.giannopoulos@gmail.comPurpose: Mean platelet volume (MPV) is a readily accessible and commonly tested hematological indicator. Recent studies revealed a significant impact of MPV on the course and prognosis of many diseases, including some types of cancer, as well as on the incidence of atrial fibrillation and bleeding. The study aimed to perform a retrospective analysis of MPV in terms of time to first treatment (TTFT) and to determine its prognostic value in the group of patients with chronic lymphocytic leukemia (CLL). Moreover, the study includes a retrospective analysis of platelet parameters in patients treated with ibrutinib concerning bleeding and atrial fibrillation.Patients and Methods: The study included 523 patients with CLL, for 344 the most important cytogenetic aberrations were reported. The Mann–Whitney, Kruskal–Wallis, Kaplan–Meier, chi-squared, log‑rank tests and multivariate Cox proportional hazard regression model were used to analyze collected data.Results: The receiver operating characteristic curve analysis was performed to identify optimal cut-off value for MPV. The analysis of survival curves showed that in the group of patients with higher values of MPV TTFT was significantly longer than in the group with lower MPV (17.9 vs 36 months, p=0.0015, cut-off value for MPV= 10.4 fl). In multivariate Cox proportional hazard regression model low MPV, the presence of del11q and del13q provided independent prognostic value for TTFT (HR=0.69, 95%-CI, 0.5293 to 0.9081; p=0.0078; HR=1.76, 95%-CI, 1.3000 to 2.3882, p=0.0003, HR=0.74, 95%-Cl, 0.5674 to 0.9588, p=0.0229, respectively). In the group treated with ibrutinib, 59 patients had no significant correlation between MPV level and the incidence of therapy complications, although in the group of patients with low MPV there was a tendency for more frequent occurrence of atrial fibrillation (p=0.259).Conclusion: Low MPV values are associated with unfavorable prognosis and might represent a novel, independent prognostic factor in CLL.Keywords: MPV, chronic lymphocytic leukemia, TTFT

Agnieszka Szymczyk,1,2 Sylwia Chocholska,1 Arkadiusz Macheta,1 Dariusz Szczepanek,3 Marek Hus,1 Monika Podhorecka11Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland; 2Department of Clinical Transplantology, Medical University of Lublin, Lublin, Poland; 3Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, Lublin, PolandBackground: Great progress has been achieved lately in the therapy for chronic lymphocytic leukemia (CLL), one of the most frequently diagnosed adult leukemias. New classes of drugs, such as kinase inhibitors and BCL-2 protein antagonists, have been approved for treatment of CLL patients. Despite the abovementioned therapies the disease can still be effectively treated with purine nucleoside analogs (PNA). However, some patients, for example, those with TP53 gene abnormalities, become resistant, and the other factors involved in the therapy resistance are still being investigated. This study was aimed at analyzing the possible role of microRNAs as markers predicting the outcome of chemotherapy based on PNA – fludarabine and cladribine in CLL patients.Methods: The expression of miR-21, miR-34a, miR-181a and miR-221 in previously separated leukemic cells was assessed with the use of qRQ-PCR technique at the moment of diagnosis in 40 CLL patients. In turn, apoptosis induced by fludarabine and cladribine in 24-hour cell culture was evaluated by determining the increase in the percentage of apoptotic cells of CD5+/CD19+/Cas3+ phenotype, using a flow cytometry method. Nine of the 40 studied subjects were treated with fludarabine-based regimens and were analyzed with regards to in vivo response to PNA.Results: We detected a significantly higher PNA-induced apoptosis rate in patients with high miR-34a expression in comparison to low expression ones. Interestingly, such differences were detected particularly in standard cytogenetic patients.Conclusions: These results may prove an important role of miR-34a expression as a predictor of apoptosis, even in cases when other risk factors like cytogenetic abnormalities are absent. An assessment of microRNAs expression seems to be useful as an indicator of sensitivity to PNA and may help to predict PNA-based therapy outcome.Keywords: chronic lymphocytic leukemia, microRNA, purine nucleoside analog, prognostic markers, apoptosis

Iminophosphoranes with the general formula (R 3 P═NR') have great potential in synthetic chemistry as valuable precursors/intermediates in organic synthesis or as building blocks for various organic compounds. However, the synthetic approaches and conditions to prepare iminophosphoranes are still poorly understood, limiting the utility of this chemistry for organic materials. In this article, a simple and efficient synthesis of previously unattainable poly(arylene iminophosphoranes) is reported. The azide-phosphine Staudinger polycondensation is used, and the reaction conditions are carefully studied, including consideration of light and air, the influence of solvent and temperature, and investigation of the electronic and steric effects of multiazides. The newly defined reaction conditions appear to be highly versatile, allowing the use of both electron-rich and electron-deficient arylazides for reaction with phosphines to synthesize a library of poly(arylene iminophosphorane) networks that exhibit exceptional thermal and oxidative stability. Interestingly, despite the ylidic-form of the iminophosphorane linkage as shown by theoretical calculations, these newly developed poly(arylene-iminophosphorane) networks exhibit semiconducting properties, such as absorption band edges up to 800 nm and optical band gaps in the range of 1.70 to 2.40 eV. Finally, we demonstrate the broad applicability of these polymers by processing them into glassy films, creating foam-like structures and synthesizing metallo-polymer hybrids., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The article discusses the production of platform chemicals from various biological sources, including glycerol, lignin, cellulose, bio-oils, and sea products. It presents the results of catalytic and downstream processes involved in the conversion of these biomass-derived feedstocks. The experimental approaches are complemented by numerical descriptions, ranging from density functional theory (DFT) calculations to kinetic modellingof the experimental data. This multi-scale modelling approach helps to understand the underlying mechanisms and optimize the production of platform chemicals from renewable resources., (Copyright 2023 Blaž Likozar, Matej Žula, Andrii Kostyniuk, Edita Jasiukaitytė-Grojzdek , Giorgio Tofani, Ramesh Kumar Chowdari, Tina Ročnik Kozmelj, Žan Lavrič, Janvit Teržan, Brigita Hočevar, Filipa A. Vicente, Ana Oberlintner, Matej Huš, Davide Benedetto Tiz, Miša Mojca Cajnko, Dana Marinič, Emilija Rakić, Brett Pomeroy, Miha Grilc, Ana Jakob, Uroš Novak. License: This work is licensed under a Creative Commons Attribution 4.0 International License.)

The selective lignin conversion into bio-based organic mono-aromatics is a major general challenge due to complex structure itself/additional macromolecule modifications, caused by the cleavage of the ether chemical bonds during the lignocellulosic biomass organosolv pulping in acidified aqueous ethanol. Herein, the acido-lysis of connected benzyl phenyl (BPE), being a representative model compound with α-O-4 linkage, was investigated in methanol, EtOH and 75 vol% EtOH/water mixture solutions, progressing each time with protonating sulfuric acid. The effect of the physical solvent properties, acidity of the reaction process media and temperature on rate was determined. Experiments suggested BPE following S N 1 mechanism due to the formation of a stable primary carbocation/polarity. The product species distribution in non-aqueous functional alcohols was strongly affected. The addition of H 2 O was advantageous, especially for alkoxylation. Yield was reduced by a factor of 3, consequently preserving reactive hydroxyl group. Quantitative experimental results indicated key performance parameters to achieve optimum. Organosolv lignins were further isolated under significantly moderate conditions. Consecutive structural differences observed supported findings, obtained when using BPE. H 2 O presence was again found to grant a higher measured -OH content. Mechanistic pathway analysis thus represents the first step when continuing to kinetics, structure-activity relationships or bio-refining industrial resources.

Accuracy of different simple interaction site water models was tested. Instead of assessing their quality through the calculations of various water physical properties (dipole moment, dielectric constant, phase-equilibria diagrams, etc.) and comparison with experimental values, we calculated water-water potential and compared it with the potential from quantum chemical calculations. Using density functional theory (DFT) water-water potential was calculated for different positions of two water molecules, which was compared with the interaction used in water models. Different simple interaction site water models were then evaluated and assessed. Special emphasis is placed on angle and distance dependence of water-water potential around minima in the potential. Among three-, four-and five-site electrostatic water models, TIP3P, TIP4P/2005 and TIP5P were found to be the most accurate.