Article
Hematology
Laura Beckmann, Valeska Berg, Clarissa Dickhut, Clare Sun, Olaf Merkel, Johannes Bloehdorn, Sandra Robrecht, Marc Seifert, Alexandra da Palma Guerreiro, Julia Claasen, Stefan Loroch, Matteo Oliverio, Chingiz Underbayev, Lauren Vaughn, Daniel Thomalla, Malte F. Huelsemann, Eugen Tausch, Kirsten Fischer, Anna Maria Fink, Barbara Eichhorst, Albert Sickmann, Clemens M. Wendtner, Stephan Stilgenbauer, Michael Hallek, Adrian Wiestner, Rene P. Zahedi, Lukas P. Frenzel
Summary: BTK inhibitors are effective in treating CLL, with potential differential effects on non-mutated versus mutated CLL cells. Ibrutinib has a stronger impact on protein phosphorylation levels in non-mutated CLL, particularly on tyrosine phosphorylation. The protein MARCKS plays a significant role in CLL diagnosis and treatment outcomes, with low expression associated with increased leukocytosis and decreased nodal disease in CLL patients.
Article
Oncology
Ti'ara L. Griffen, Fieke W. Hoff, Yihua Qiu, James W. Lillard, Alessandra Ferrajoli, Philip Thompson, Endurance Toro, Kevin Ruiz, Jan Burger, William Wierda, Steven M. Kornblau
Summary: This study is the largest CLL proteomics study to date, assessing protein expression in 384 total and post-translationally modified proteins in 871 CLL and MSBL patients. The study identified six recurrent signatures that were highly prognostic of survival and time to treatment. These findings have important implications for improving diagnostics and therapy for CLL.
BLOOD CANCER JOURNAL
(2022)
Article
Multidisciplinary Sciences
Jae Sung Ko, Dongjin Jeong, Jaemoon Koh, Hyeryeon Jung, Kyeong Cheon Jung, Yoon Kyung Jeon, Hye Young Kim, Eugene C. Yi, Ho Lee, Chang-Woo Lee, Doo Hyun Chung
Summary: Ssu72 regulates the fine-tuning of TCR signaling by acting as a tyrosine phosphatase for ZAP-70. Ssu72 deficiency leads to hyperresponsiveness in T cells upon TCR stimulation due to increased ZAP-70 phosphorylation, which can be restored by reducing ZAP-70 phosphorylation levels. Additionally, Cd4-CreSsu72fl/fl mice show defects in thymic development and alterations in peripheral T cell populations, with a predisposition for spontaneous inflammation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Oncology
Aneel Paulus, Fabio Malavasi, Asher Chanan-Khan
Summary: CD38 plays a role in CLL pathogenesis and its increased expression is associated with poor prognosis. This review focuses on the functions of CD38 in CLL cell survival and the mechanisms of leukemic cell death induced by anti-CD38 therapies. It also discusses the potential of targeting CD38 for immunotherapy and the development of novel strategies.
LEUKEMIA & LYMPHOMA
(2022)
Article
Pathology
Richa Gupta, Neha Garg, Abha Singh, Shyam Jain
Summary: This study investigated the prevalence of ZAP-70 and its association with other prognostic markers in Indian CLL patients. The results found a low prevalence rate of ZAP-70 and no association with conventional poor prognostic factors. Most patients were in the good prognostic group, suggesting a favorable prognosis and good overall survival. Geographical variations, genetic makeup, and natural history may contribute to these differences.
INDIAN JOURNAL OF PATHOLOGY AND MICROBIOLOGY
(2023)
Article
Chemistry, Medicinal
Danni Rao, Heng Li, Xuelian Ren, Yaoliang Sun, Cuiyun Wen, Mingyue Zheng, He Huang, Wei Tang, Shilin Xu
Summary: ZAP-70 signaling pathway is crucial in T cell development and immune response, making it a promising target for autoimmune disease treatment. The development of a selective and potent covalent inhibitor of ZAP-70 kinase domain shows promising inhibitory effects on T cell activation and inflammatory response.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ming-Tai Hu, Wen-Cong Ma, Jing-Han Wang, Xiao-Qing Jiang, Da-Qing Yang, Jian-Yang Ao
Summary: ZAP-70 is a non-receptor tyrosine kinase that interacts with the activated T-cell receptor to transmit downstream signals. This study investigates the molecular mechanisms of allosteric inactivation of ZAP-70 induced by the W165C mutation, which reveals changes in protein dynamics and binding affinity. The findings provide insights into the pathological mechanism of ZAP-70.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Immunology
Diana Martin, Pedro Perdiguero, Esther Morel, Irene Soleto, J. German Herranz-Jusdado, Luis A. Ramon, Beatriz Abos, Tiehui Wang, Patricia Diaz-Rosales, Carolina Tafalla
Summary: CD38 has diverse expressions in different species, with high levels in mouse B cell subsets and transient expression on early lymphocyte precursors in humans while consistently expressed on terminally differentiated plasma cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Andreas Agathangelidis, Anastasia Chatzidimitriou, Thomas Chatzikonstantinou, Cristina Tresoldi, Zadie Davis, Veronique Giudicelli, Sofia Kossida, Chrysoula Belessi, Richard Rosenquist, Paolo Ghia, Anton W. Langerak, Frederic Davi, Kostas Stamatopoulos
Summary: The somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy variable (IGHV) gene is critical for assessing prognosis and responses to therapy in patients with chronic lymphocytic leukemia (CLL). Immunogenetic analysis in CLL has also revealed distinct subsets of patients based on (quasi)identical B cell receptor immunoglobulin (BcR IG), which display consistent biology, clinical presentation, and outcome. As a cornerstone for accurate risk stratification and clinical decision making, immunogenetic analysis in CLL requires robust methodologies, including next generation sequencing (NGS).
Review
Immunology
Inhye E. Ahn, Jennifer R. Brown
Summary: Targeting the B-cell receptor signaling pathway through BTK inhibition has shown significant efficacy in the treatment of CLL and B-cell lymphomas. Different selectivity of individual BTKis leads to differences in target-mediated and off-target adverse effects. Disease progression driven by histologic transformation or selective expansion of mutated CLL clones remains a major challenge, but new combination regimens and reversible BTKis hold promise for preventing and treating BTKi-resistant disease.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Marcin Domagala, Loic Ysebaert, Laetitia Ligat, Frederic Lopez, Jean-Jacques Fournie, Camille Laurent, Mary Poupot
Summary: In chronic lymphocytic leukemia, M2-like nurse-like cells (NLC) provide protection against apoptosis for leukemic cells through the release of IL-10, while M1-like NLC do not have this effect. The balance between IL-10 and TNF plays an important role in maintaining the protective phenotype of NLCs and the survival of CLL cells.
Article
Cell Biology
Ramin Sedaghat Herati, Luisa Victoria Silva, Laura A. Vella, Alexander Muselman, Cecile Alanio, Bertram Bengsch, Raj K. Kurupati, Senthil Kannan, Sasikanth Manne, Andrew Kossenkov, David H. Canaday, Susan A. Doyle, Hildegund C. J. Ertl, Kenneth E. Schmader, E. John Wherry
Summary: The study found that after influenza vaccination, ICOS(+)CD38(+) cTfh cells in the blood of elderly individuals were enriched in gene sets associated with youth, and these cells had increased expression of genes associated with inflammation compared to other circulating T cell types. These data highlight the potential use of vaccine-induced cTfh as cellular biosensors for underlying inflammatory and immune health status.
CELL REPORTS MEDICINE
(2021)
Article
Chemistry, Medicinal
Victor Masip, Angel Lirio, Albert Sanchez-Lopez, Ana B. Cuenca, Raimon Puig de la Bellacasa, Pau Abrisqueta, Jordi Teixido, Jose Borrell, Albert Gibert, Roger Estrada-Tejedor
Summary: Pyrido[2,3-d]pyrimidin-7(8H)-ones have drawn widespread interest as tyrosine kinase inhibitors, with a general synthetic methodology described for the synthesis of 4-substituted-2-(phenylamino)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones. The resulting compounds, including N-alkyl, N-aryl, O-aryl, S-aryl, aryl, and aryethynyl substituents at C4, have shown potential biological activity as ZAP-70 inhibitors.
Article
Allergy
Gui-Xiang Tian, Ke-Ping Peng, Ming-Hui Liu, Dao-Fa Tian, Hai-Qing Xie, Li-Wen Wang, Yu-Yang Guo, Shan Zhou, Li-Hua Mo, Ping-Chang Yang
Summary: This study found that a fraction of antigen-specific CD38(+) B cells were present in patients with perennial allergic rhinitis. These cells produce IL-6, which converts regulatory T cells into TH17 cells, thereby compromising the effects of allergen-specific immunotherapy. Inhibition of CD38(+) B cells enhances the effects of immunotherapy.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xuehua Zhang, Wenqi Liang, Guodong Zheng, Bei Li
Summary: In this study, multiple replica molecular dynamics simulations and the MM-GBSA method were used to reveal the deactivation mechanism of ZAP-70 induced by the R192W mutation mediated by doubly phosphorylated ITAMs (ITAM-Y2P).
JOURNAL OF MOLECULAR MODELING
(2023)
Article
Multidisciplinary Sciences
Beata Kasztelan-Szczerbinska, Katarzyna Adamczyk, Agata Surdacka, Jacek Rolinski, Agata Michalak, Agnieszka Bojarska-Junak, Mariusz Szczerbinski, Halina Cichoz-Lach
Summary: This study found gender-related differences in the frequencies of PD-1/PD-L1 positive T and B cells in patients with ALD. Upregulation of PD-1+/PD-L1+ lymphocytes paralleled both the severity of alcoholic hepatitis and liver dysfunction in ALD females.
Article
Biochemistry & Molecular Biology
Malgorzata Sobstyl, Paulina Niedzwiedzka-Rystwej, Rafal Hrynkiewicz, Dominika Bebnowska, Izabela Korona-Glowniak, Marcin Pasiarski, Barbara Sosnowska-Pasiarska, Jolanta Smok-Kalwat, Stanislaw Gozdz, Anna Sobstyl, Wojciech Polkowski, Jacek Rolinski, Ewelina Grywalska
Summary: The study demonstrated the significance of TLR2 as a biomarker in advanced stage ovarian cancer by showing significantly higher expression levels in women with more advanced OC. This research sheds light on the prognostic potential of TLR2 in developing new diagnostic approaches and increasing survival in confirmed ovarian cancer patients.
Article
Cell Biology
Lidia Karabon, Anna Andrzejczak, Lidia Ciszak, Anna Tomkiewicz, Aleksandra Szteblich, Agnieszka Bojarska-Junak, Jacek Rolinski, Dariusz Wolowiec, Tomasz Wrobel, Agata Kosmaczewska
Summary: Our study reveals that miR-155-5p is involved in BTLA deficiency, affecting the proliferation of CLL B cells, which may be one of the mechanisms responsible for CLL pathogenesis.
Article
Cell Biology
Michal K. Zarobkiewicz, Agnieszka A. Bojarska-Junak
Summary: CLL is the most common leukemia among adults, and currently there is no cure. Despite the dysfunction of gamma delta T cells in CLL patients, they can still be used for immunotherapy.
Article
Biochemistry & Molecular Biology
Wioleta Kowalska, Michal Zarobkiewicz, Waldemar Tomczak, Justyna Wos, Izabela Morawska, Agnieszka Bojarska-Junak
Summary: Monocytes, particularly non-classical subpopulations, may play an important role in chronic lymphocytic leukemia (CLL) pathogenesis. This study assessed monocyte subsets divided based on SLAN and CD16 expression in CLL patients. The findings suggest an increased percentage of non-classical monocytes producing TNF and IL-12, while intermediate monocytes showed a higher percentage of cells synthesizing anti-inflammatory IL-10. The percentage of CD14(dim)CD16(+)SLAN(+) monocytes producing TNF and IL-12 decreased with CLL stage and correlated with prognostic factors. Notably, CLL patients requiring treatment had a lower percentage of CD14(dim)CD16(+)SLAN(+) monocytes producing TNF and IL-12, potentially indicating a beneficial effect of non-classical monocytes on anti-tumor response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Ewelina Firlej, Wioleta Kowalska, Karolina Szymaszek, Jacek Rolinski, Joanna Bartosinska
Summary: Acne vulgaris is a common skin disease caused by multiple factors and inflammation. Recent studies have found that skin immune cells play a significant role in the course of the disease.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Neurosciences
Jakub Litak, Wieslawa Grajkowska, Jacek Bogucki, Pawel Kowalczyk, Alicja Petniak, Arkadiusz Podkowinski, Justyna Szumilo, Janusz Kocki, Jacek Rolinski, Mansur Rahnama-Hezavah, Marcin Roszkowski, Cezary Grochowski
Summary: High-grade pediatric glioma is a common malignancy in children. This study found a significant correlation between miR-155 concentration and PD-L1 expression in tumor tissue.
Article
Medicine, General & Internal
Michal K. Zarobkiewicz, Izabela Morawska, Wioleta Kowalska, Pawel Halczuk, Jacek Rolinski, Agnieszka A. Bojarska-Junak
Summary: This study found differential expression of PECAM-1 on γδT cells and a significant downregulation of CD3 expression during relapse in patients with multiple sclerosis, which may indicate overall activation of γδT cells.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Medicine, General & Internal
Violetta Opoka-Winiarska, Ewelina Grywalska, Izabela Korona-Glowniak, Izabela Morawska, Krzysztof Gosik, Anna Malm, Jacek Rolinski
Summary: This study aimed to evaluate the impact of COVID-19 disease on patients with childhood rheumatic diseases. The study found significantly higher levels of SARS-CoV-2 antibodies in JIA patients compared to the control group, and these levels were correlated with the serological response to SARS-CoV-2. Additionally, serum PD-1 levels were also significantly higher in JIA patients and control volunteers who were seropositive for SARS-CoV-2 antibodies. The findings highlight the need for further observation of these detected abnormalities.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Cell Biology
Paulina Niedzwiedzka-Rystwej, Adam Majchrzak, Bogusz Aksak-Was, Karol Serwin, Zenon Czajkowski, Ewelina Grywalska, Izabela Korona-Glowniak, Jacek Rolinski, Milosz Parczewski
Summary: Current research shows that immune dysregulation and immune exhaustion are common in COVID-19, and markers of disease severity may include immune checkpoint molecules such as PD-1 and PD-L1. This study evaluated the expression of PD-1/PD-L1 in COVID-19 patients and found that increased PD-1+ and PD-L1+ lymphocytes are associated with disease severity and mortality.
Review
Oncology
Jakub Litak, Wojciech Czyzewski, Michal Szymoniuk, Leon Sakwa, Barbara Pasierb, Joanna Litak, Zofia Hoffman, Piotr Kamieniak, Jacek Rolinski
Summary: Spine metastases are a common and life-threatening complication of advanced-stage malignancies, often with a poor prognosis. Understanding metastatic processes is crucial in order to find targeted therapeutic options. The current literature provides knowledge about molecular pathways and biomarkers involved in spine metastases, as well as current and emerging treatment options.
Article
Biochemistry & Molecular Biology
Sylwia Chocholska, Michal Zarobkiewicz, Agata Szymanska, Natalia Lehman, Justyna Wos, Agnieszka Bojarska-Junak
Summary: The aim of this study was to investigate the expression of miR-17 similar to 92 cluster members in CLL patients. The study provides new evidence regarding the heterogeneity of miR-17 similar to 92 cluster members' expression in CLL patients. High miR-20a expression can be considered an independent favorable prognostic factor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Natalia Lehman, Wioleta Kowalska, Michal Zarobkiewicz, Marek Mazurek, Karolina Mrozowska, Agnieszka Bojarska-Junak, Radoslaw Rola
Summary: Monocyte subpopulations in glioma patients' peripheral blood were analyzed based on CD14, CD16, and SLAN expression. The study found different profiles of monocytes with varying cytokine expression. The presence of these different profiles might hinder the effectiveness of immunotherapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Agnieszka Bojarska-Junak, Wioleta Kowalska, Sylwia Chocholska, Agata Szymanska, Waldemar Tomczak, Michal Konrad Zarobkiewicz, Jacek Rolinski, Daniela De Totero, Paolo Giannoni
Summary: This study explores the potential role of Galectin-9 (Gal-9) as a novel prognostic biomarker in chronic lymphocytic leukemia (CLL). Through quantification of Gal-9 mRNA expression in purified B-lymphocytes of 100 CLL patients, the study reveals the upregulation of Gal-9 mRNA in malignant B-cells, which is closely associated with unfavorable prognostic markers and a shorter time to treatment. Furthermore, the study suggests that EBV coinfection may worsen prognosis in CLL by inducing upregulation of Gal-9 expression.
