المؤلفون: Zmorzynski, Szymon, Popek-Marciniec, Sylwia, Biernacka, Beata, Szudy-Szczyrek, Aneta, Chocholska, Sylwia, Styk, Wojciech, Czerwik-Marcinkowska, Joanna, Swiderska-Kolacz, Grazyna

المصدر: Genes (Basel) ; ISSN:2073-4425 ; Volume:15 ; Issue:3

مصطلحات موضوعية: apoptosis, bortezomib, glutathione S-transferase, glutathione peroxidase, glutathione reductase, multiple myeloma, reduced glutathione

الوصف: Multiple myeloma (MM) is a malignancy derived from plasma cells. Bortezomib affects the concentration of reduced glutathione (GSH) and the activity of glutathione enzymes. The aim of our study was to analyze deletion (null/present) variants of GSTT1 and GSTM1 genes and their association with the levels of glutathione and its enzymes in bortezomib-treated cell cultures derived from MM patients.

العلاقة: https://doi.org/10.3390/genes15030387Test; https://pubmed.ncbi.nlm.nih.gov/38540446Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10970692Test/

الإتاحة: https://doi.org/10.3390/genes15030387Test
https://pubmed.ncbi.nlm.nih.gov/38540446Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10970692Test/

المؤلفون: Woś, Justyna, Szymańska, Agata, Lehman, Natalia, Chocholska, Sylwia, Zarobkiewicz, Michał, Pożarowski, Piotr, Bojarska-Junak, Agnieszka

المصدر: Cells (2073-4409); Jan2024, Vol. 13 Issue 1, p30, 18p

مصطلحات موضوعية: CHRONIC lymphocytic leukemia, GALECTINS, BIOMARKERS, BCL-2 proteins, GENE expression

مستخلص: Galectin-3's (Gal-3) effect on the pathogenesis of chronic lymphocytic leukemia (CLL) has not yet been extensively studied. The present study aims to analyze the potential role of Gal-3 as a prognostic biomarker in CLL patients. The Gal-3 expression was evaluated in CLL cells with RT-qPCR and flow cytometry. Due to the unclear clinical significance of soluble Gal-3 in CLL, our goal was also to assess the prognostic value of Gal-3 plasma level. Because cell survival is significantly affected by the interaction between Gal-3 and proteins such as Bcl-2, the results of Gal-3 expression analysis were also compared with the expression of Bcl-2. The results were analyzed for known prognostic factors, clinical data, and endpoints such as time to first treatment and overall survival time. Our research confirmed that Gal-3 is detected in and on CLL cells. However, using Gal-3 as a potential biomarker in CLL is challenging due to the significant heterogeneity in its expression in CLL cells. Moreover, our results revealed that Gal-3 mRNA expression in leukemic B cells is associated with the expression of proliferation markers (Ki-67 and PCNA) as well as anti-apoptotic protein Bcl-2 and can play an important role in supporting CLL cells. [ABSTRACT FROM AUTHOR]

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المؤلفون: Bojarska-Junak, Agnieszka, Kowalska, Wioleta, Chocholska, Sylwia, Szymańska, Agata, Tomczak, Waldemar, Zarobkiewicz, Michał Konrad, Roliński, Jacek

المصدر: Cancers; Nov2023, Vol. 15 Issue 22, p5370, 17p

مصطلحات موضوعية: PROTEIN metabolism, CHRONIC lymphocytic leukemia, DISEASE progression, REVERSE transcriptase polymerase chain reaction, TIME, REGULATORY B cells, GENE expression, MESSENGER RNA, EPSTEIN-Barr virus, MIXED infections, GENE expression profiling, RESEARCH funding, DESCRIPTIVE statistics, TUMOR markers, PREDICTIVE validity

مستخلص: Simple Summary: There are still very few studies on Galectin-9 (Gal-9) in chronic lymphocytic leukemia (CLL), and the effect of Gal-9 on CLL pathogenesis. This study considers the possible role of Gal-9 as a new prognostic biomarker in CLL. Gal-9 mRNA expression was quantified with RT-qPCR in purified B-lymphocytes of 100 CLL patients and analyzed in the context of clinical data. Our results revealed the upregulation of Gal-9 mRNA in malignant B-cells. Unfavorable prognostic markers were closely linked to high Gal-9 mRNA expression. An increase in Gal-9 mRNA expression was also correlated with a shorter time to treatment. Gal-9 plays a crucial role in the tumor microenvironment and may become a significant complement to other prognostic indicators. Furthermore, we propose that EBV coinfection may have a detrimental effect on the prognosis of CLL patients, partly due to Gal-9 expression upregulation caused by EBV. Galectin-9 (Gal-9), very poorly characterized in chronic lymphocytic leukemia (CLL), was chosen in our study to examine its potential role as a CLL biomarker. The relation of Gal-9 expression in malignant B-cells and other routinely measured CLL markers, as well as its clinical relevance are poorly understood. Gal-9 mRNA expression was quantified with RT-qPCR in purified CD19+ B-cells of 100 CLL patients and analyzed in the context of existing clinical data. Our results revealed the upregulation of Gal-9 mRNA in CLL cells. High Gal-9 mRNA expression was closely associated with unfavorable prognostic markers. In addition, Gal-9 expression in leukemic cells was significantly elevated in CLL patients who did not respond to the first-line therapy compared to those who did respond. This suggests its potential predictive value. Importantly, Gal-9 was an independent predictor for the time to treatment parameters. Thus, we can suggest an adverse role of Gal-9 expression in CLL. Interestingly, it is possible that Gal-9 expression is induced in B-cells by EBV infection, so we determined the patients' EBV status. Our suggestion is that EBV coinfection could worsen prognosis in CLL, partly due to Gal-9 expression upregulation caused by EBV. [ABSTRACT FROM AUTHOR]

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المؤلفون: Popek-Marciniec, Sylwia, Styk, Wojciech, Wojcierowska-Litwin, Magdalena, Chocholska, Sylwia, Szudy-Szczyrek, Aneta, Samardakiewicz, Marzena, Swiderska-Kolacz, Grazyna, Czerwik-Marcinkowska, Joanna, Zmorzynski, Szymon

المصدر: Cancers; Oct2023, Vol. 15 Issue 19, p4747, 16p

مصطلحات موضوعية: RNA analysis, DNA analysis, CHROMOSOMES, PROTEINS, REVERSE transcriptase polymerase chain reaction, THALIDOMIDE, GENETIC mutation, SEQUENCE analysis, ONCOGENES, NON-smokers, BORTEZOMIB, TREATMENT effectiveness, GENE expression, PEARSON correlation (Statistics), GENOMICS, FISHES, GENOTYPES, DESCRIPTIVE statistics, RESEARCH funding, MULTIPLE myeloma, DISEASE risk factors

مستخلص: Simple Summary: The detailed role of the TP53 p.P72R (rs1042522) variant in the etiology and course of multiple myeloma (MM), as well as its association with chromosome 17 aberrations, has not been analyzed in a such a wide range. In our study, we have explored the significance of the p.P72R variant, expression level of TP53 gene, deletion of TP53 locus and chromosome 17 aneuploidies in MM development, and the response to bortezomib/thalidomide treatment in MM patients. We have shown that the p.R72R variant was associated with a higher age of MM patients at diagnosis and with a higher number of plasma cells. We have found higher expression of TP53 in MM smokers in comparison to MM non-smokers. TP53 gene expression and the p.P72R variant did not affect the MM outcome. Multiple myeloma (MM) is a multifactorial genetic disorder caused by interactive effects of environmental and genetic factors. The proper locus of the TP53 gene (17p13.1) and its protein is essential in genomic stability. The most common variant of the TP53 gene—p.P72R (rs1042522)—shows functional variation. The aim of our study was a complex analysis of the TP53 p.P72R variant and TP53 gene expression in relation to chromosomal changes of the TP53 gene locus, as well as MM risk and outcome. Genomic DNA from 129 newly diagnosed MM patients was analyzed by methods of automated DNA sequencing (for TP53 variant analysis) and cIg-FISH (for chromosomal aberrations analysis). RNA was used in real-time PCR to determine the TP53 expression. In MM patients, the TP53 variant was not in Hardy–Weinberg equilibrium. The RR genotype was associated with lower MM risk (OR = 0.44, p = 0.004). A higher number of plasma cells was found in patients with RR genotype in comparison to those with PP + PR genotypes (36.74% vs. 28.30%, p = 0.02). A higher expression of the TP53 gene was observed in PP + PR genotypes vs. RR homozygote (p < 0.001), in smokers vs. non-smokers (p = 0.02). A positive Pearson's correlation was found between the TP53 expression level and the number of plasma cells (r = 0.26, p = 0.04). The presence of chromosome 17 aberrations with or without TP53 locus did not affect the MM risk and outcome. Similar results were observed in the case of TP53 gene expression and the p.P72R variant. [ABSTRACT FROM AUTHOR]

: Copyright of Cancers is the property of MDPI 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.)

المؤلفون: Szymczyk,Agnieszka, Chocholska,Sylwia, Macheta,Arkadiusz, Szczepanek,Dariusz, Hus,Marek, Podhorecka,Monika

مصطلحات موضوعية: Cancer Management and Research

الوصف: 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 ...

وصف الملف: text/html

العلاقة: https://www.dovepress.com/assessment-of-microrna-expression-in-leukemic-cells-as-predictors-of-s-peer-reviewed-fulltext-article-CMARTest

الإتاحة: https://doi.org/10.2147/CMAR.S191311Test
https://www.dovepress.com/assessment-of-microrna-expression-in-leukemic-cells-as-predictors-of-s-peer-reviewed-fulltext-article-CMARTest

المؤلفون: Szymczyk, Agnieszka, Chocholska, Sylwia, Macheta, Arkadiusz, Szczepanek, Dariusz, Hus, Marek, Podhorecka, Monika

المصدر: Cancer Management and Research ; volume Volume 11, page 5021-5031 ; ISSN 1179-1322

الإتاحة: https://doi.org/10.2147/cmar.s191311Test
https://www.dovepress.com/getfile.php?fileID=50221Test

المؤلفون: Zmorzynski, Szymon, Szudy-Szczyrek, Aneta, Popek-Marciniec, Sylwia, Korszen-Pilecka, Iwona, Wojcierowska-Litwin, Magdalena, Luterek, Małgorzata, Chocholska, Sylwia, Styk, Wojciech, Swiderska-Kołacz, Grazyna, Januszewska, Joanna, Mielnik, Michal, Hus, Marek, Filip, Agata A.

المصدر: Frontiers in Oncology ; volume 9 ; ISSN 2234-943X

الإتاحة: https://doi.org/10.3389/fonc.2019.00044Test

المؤلفون: Zmorzyński, Szymon, Popek-Marciniec, Sylwia, Szudy-Szczyrek, Aneta, Wojcierowska-Litwin, Magdalena, Korszeń-Pilecka, Iwona, Chocholska, Sylwia, Styk, Wojciech, Hus, Marek, Filip, Agata A.

المصدر: Frontiers in Oncology ; volume 9 ; ISSN 2234-943X

مصطلحات موضوعية: Cancer Research, Oncology

الإتاحة: https://doi.org/10.3389/fonc.2019.01056Test

المؤلفون: Szudy-Szczyrek, Aneta, Mlak, Radosław, Mazurek, Marcin, Krajka, Tomasz, Chocholska, Sylwia, Bitkowska, Paulina, Jutrzenka, Marta, Szczyrek, Michał, Homa-Mlak, Iwona, Krajka, Andrzej, Małecka-Massalska, Teresa, Hus, Marek

المصدر: Cells (2073-4409); Apr2023, Vol. 12 Issue 7, p1029, 16p

مصطلحات موضوعية: MULTIPLE myeloma, HEMATOPOIETIC stem cell transplantation, GENOTYPES, PROGNOSIS, PROGRESSION-free survival

مستخلص: Background: The KIAA1524 gene encodes an oncoprotein, CIP2A, which inhibits the phosphorylation of the Akt kinase B, stabilizes the c-Myc protein, and, through that, promotes cancerogenesis. An increase in CIP2A expression has been observed in numerous solid tumors and hematologic malignancies, including multiple myeloma (MM). The aim of our study was to evaluate the clinical impact of the functional single nucleotide polymorphisms (SNP) of the KIAA1524 gene (rs2278911, 686C > T) in MM patients. Methods: The study group consisted of 128 patients with de novo MM. EDTA venous blood samples were collected prior to the treatment. The SNPs were analyzed by Real-Time PCR with the use of specific Taqman probes. Results: Multivariable analysis revealed that variables independently associated with shorter progression-free survival (PFS) included thrombocytopenia, delTP53 and IGH/CCND1 translocation and the TT genotype of the KIAA1524 gene (686C > T) (median PFS: 6 vs. 25 months; HR = 7.18). On the other hand, autologous haematopoietic stem cell transplantation (AHSCT) was related to a lower risk of early disease progression. Moreover, light chain disease, International Staging System (ISS) 3, poor performance status, hypoalbuminemia, IGH/FGFR3 translocation and the TT genotype of the KIAA1524 gene (686C > T) were independent prognostic factors associated with shorter overall survival (OS) (median OS: 8 vs. 45 months; HR = 7.08). Conclusion: The evaluation of the SNP 686C > T of the KIAA1524 gene could be used as a diagnostic tool in MM patients at risk of early disease progression and death. [ABSTRACT FROM AUTHOR]

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المؤلفون: Chocholska, Sylwia¹ (AUTHOR), Zarobkiewicz, Michał² (AUTHOR), Szymańska, Agata³ (AUTHOR), Lehman, Natalia² (AUTHOR), Woś, Justyna² (AUTHOR), Bojarska-Junak, Agnieszka² (AUTHOR) agnieszkabojarskajunak@umlub.pl

المصدر: International Journal of Molecular Sciences. Jan2023, Vol. 24 Issue 2, p1705. 17p.

مصطلحات موضوعية: *CHRONIC lymphocytic leukemia, *PROGNOSIS, *GENE expression, *B cells, *TUMOR markers

مستخلص: The aim of this study was to investigate the expression of miR-17∼92 cluster members in chronic lymphocytic leukemia (CLL) patients. Six microRNAs (miRNAs)—miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1—very poorly characterized in CLL patients, were chosen for the study to consider their possible role as cancer biomarkers. It is currently unclear to which extent miR-17~92 expression is related to other routinely measured CLL markers, and whether the findings can be of any clinical significance. To achieve this goal, we report the expression levels of these miRNAs detected by RT-qPCR in purified CD19+ B lymphocytes of 107 CLL patients and correlate them with existing clinical data. The study provides new evidence regarding the heterogeneity of miR-17~92 cluster members' expression in CLL patients. Higher miR-17-5p expression was associated with unfavorable prognostic factors (i.e., 17p and 11q deletions, CD38 and ZAP-70 expression). On the other hand, miR-19a, miR-20a, and miR-92a-1 negatively correlated with these adverse factors. The presence of del(13q) as a sole aberration was associated with a significantly lower miR-17-5p as well as higher miR-19a-3p and miR-92a-1-5p expression compared to patients carrying unfavorable genetic aberrations. Particularly, miR-20a could be considered an independent favorable prognostic factor. In a multivariate analysis, high miR-20a expression remained an independent marker predicting long TTT (time to treatment) for CLL patients. [ABSTRACT FROM AUTHOR]