Article
Cell Biology
Fangfang Wang, Zhang Dan, Hongmei Luo, Jingcao Huang, Yushan Cui, Hong Ding, Juan Xu, Zhimei Lin, Yuhan Gao, Xinyu Zhai, Yan Yang, Ying Qu, Li Zhang, Fengjiao Chen, Qiang Wang, Xin Wang, Yu Feng, Ting Liu, Qing Yi, Ting Niu, Yuhuan Zheng
Summary: Drug-resistance is a major problem in multiple myeloma (MM) patients. This study reveals that activated-leukocyte-cell-adhesion-molecule (ALCAM) regulates MM side population (SP)-mediated drug-resistance through the ALCAM-EGF/EGFR axis. EGFR activation promotes the SP ratio, while ALCAM inhibits EGFR downstream signaling in MM cells. SP MM cells have a higher number of mitochondria and interference of mitochondrial function inhibits SP-genesis. Combination therapy with an anti-MM agent and EGFR inhibitor gefitinib improves MM therapeutic efficacy and prolongs survival in MM-bearing mice.
CELL DEATH & DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Divya M. Teli, Anuradha K. Gajjar
Summary: Elevated glucose level due to β-cell dysfunction is a key marker of Type-II diabetes. GSK-3, an enzyme involved in glycogen metabolism control, has been explored for its potential as a target for diabetes treatment. This review article examines the structural analysis and molecular modeling of GSK-3, as well as advancements in the development of GSK-3 inhibitors as potential therapeutics for Type II diabetes.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Pegah Abdollahi, Esten N. Vandsemb, Samah Elsaadi, Lisa M. Rost, Rui Yang, Magnus A. Hjort, Trygve Andreassen, Kristine Misund, Tobias S. Slordahl, Torstein B. Ro, Anne-Marit Sponaas, Siver Moestue, Per Bruheim, Magne Borset
Summary: PRL-3, a cytokine-induced oncogenic phosphatase highly expressed in multiple myeloma cells, influences metabolism by promoting aerobic glycolysis, glucose uptake, and increasing levels of proteins regulating glycolysis and enzymes in the serine/glycine synthesis pathway. Important metabolic effects of PRL-3 are independent of its phosphatase activity, with glycine decarboxylase (GLDC) playing a significant role in PRL-3-induced aerobic glycolysis.
Article
Hematology
Brittany C. Lipchick, Adam Utley, Zhannan Han, Sudha Moparthy, Dong Hyun Yun, Anna Bianchi-Smiraglia, David W. Wolff, Emily Fink, Liang Liu, Cristina M. Furdui, Jingyun Lee, Kelvin P. Lee, Mikhail A. Nikiforov
Summary: This study identified the role of lipid metabolism in the resistance of multiple myeloma cells to the proteasome inhibitor bortezomib. Lower levels of fatty acid elongase 6 (ELOVL6) were found in bortezomib-nonresponsive MM cells compared to bortezomib-responsive cells. Restoring ELOVL6 levels resensitized resistant cells by upregulating ceramide species, essential for bortezomib-induced endoplasmic reticulum stress and cell death.
Article
Neurosciences
Elena Kisseleff, Robin J. Vigouroux, Catherine Hottin, Sophie Lourdel, Leah Thomas, Parth Shah, Alain Chedotal, Muriel Perron, Anand Swaroop, Jerome E. Roger
Summary: The study reveals a unique role of GSK3 in controlling the production of ganglion cells in the inner nuclear layer, corresponding to dRGCs, a rare and poorly characterized retinal cell type. In Gsk3 mutant mice, an excess of dRGCs leads to more axons projecting into the non-image-forming visual circuit, and at least a subset of dRGCs are direction-selective RGCs.
Article
Fisheries
Xiaotong Sun, Hongtao Nie, Xiwu Yan
Summary: This study identified and investigated three novel glycogen metabolism-related proteins in Manila clam, suggesting their potential involvement in innate immunity and important role in immune defense.
Article
Medicine, General & Internal
Pieter Sonneveld, Meletios A. Dimopoulos, Mario Boccadoro, Hang Quach, P. Joy Ho, Meral Beksac, Cyrille Hulin, Elisabetta Antonioli, Xavier Leleu, Silvia Mangiacavalli, Aurore Perrot, Michele Cavo, Angelo Belotti, Annemiek Broijl, Francesca Gay, Roberto Mina, Inger S. Nijhof, Niels W. C. J. van de Donk, Eirini Katodritou, Fredrik Schjesvold, Anna Sureda Balari, Laura Rosinol, Michel Delforge, Wilfried Roeloffzen, Tobias Silzle, Annette Vangsted, Hermann Einsele, Andrew Spencer, Roman Hajek, Artur Jurczyszyn, Sarah Lonergan, Tahamtan Ahmadi, Yanfang Liu, Jianping Wang, Diego Vieyra, Emilie M. J. van Brummelen, Veronique Vanquickelberghe, Anna Sitthi-Amorn, Carla J. de Boer, Robin Carson, Paula Rodriguez-Otero, Joan Blade, Philippe Moreau
Summary: The addition of subcutaneous daratumumab to VRd induction and consolidation therapy and to lenalidomide maintenance therapy showed significant improvement in progression-free survival among transplantation-eligible patients with newly diagnosed multiple myeloma.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Biotechnology & Applied Microbiology
Tomoyuki Furuya, Ryuichi Nishihama, Kimitsune Ishizaki, Takayuki Kohchi, Hiroo Fukuda, Yuki Kondo
Summary: Plants maintain continuous development by precisely balancing cell proliferation and differentiation. A study on the liverwort Marchantia polymorpha revealed that MpGSK, a member of the GSK3 kinase family, plays an important role in regulating cell differentiation and proliferation.
PLANT BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jing Guo, Yangyang Lv, Sheng Wang, Ziyi Peng, Ying Xie, Yixuan Wang, Hongmei Jiang, Xin Li, Mengqi Wang, Meilin Hu, Jiangpeng Mu, Jingya Wang, Yangyang Xie, Xiankui Cheng, Zhigang Zhao, Zhiqiang Liu
Summary: The hypoxic bone marrow microenvironment in multiple myeloma (MM) promotes chemoresistance to proteasome inhibitors (PIs). The expression of steroid receptor coactivator 3 (SRC-3) is increased at the posttranslational level in response to hypoxia stimulus. SENP1, a key modifier of SRC-3 stability, is identified and its depletion or inhibition overcomes chemoresistance to PIs in MM cells.
Article
Engineering, Biomedical
Di Wu, Zongyi Wang, Jun Li, Yan Song, Manuel Everardo Mondragon Perez, Zixuan Wang, Xia Cao, Changliang Cao, Sushila Maharjan, Kenneth C. Anderson, Dharminder Chauhan, Yu Shrike Zhang
Summary: This study describes the fabrication of a high-content in vitro multiple myeloma (MM) model using a coaxial extrusion bioprinting method, which can simulate the human bone marrow microenvironment and shows that MM cells cultured in 3D models are more sensitive to drugs.
ADVANCED HEALTHCARE MATERIALS
(2022)
Review
Biochemistry & Molecular Biology
Chia-Ling Chen, Po-Chun Tseng, Rahmat Dani Satria, Thi Thuy Nguyen, Cheng-Chieh Tsai, Chiou-Feng Lin
Summary: GSK-3 is a vital regulator of glycogen synthesis that plays a crucial role in cellular bioregulation. Abnormal GSK-3 activation and inactivation can lead to liver damage. Targeting GSK-3 with drugs is a potential therapeutic approach for liver protection. Additionally, blocking GSK-3 has a protective effect in IFN-gamma-mediated immune hepatitis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Izabela Gutowska, Agnieszka Maruszewska, Marta Skorka-Majewicz, Agnieszka Kempinska-Podhorodecka, Agnieszka Kolasa, Agata Wszolek, Irena Baranowska-Bosiacka, Wojciech Zwierello
Summary: Human exposure to fluorine from multiple sources can lead to metabolic disorders, particularly in muscle cells. This study investigated the impact of fluoride exposure on enzymes involved in muscle glycogen metabolism. It was found that fluoride exposure altered energy state, enzyme expression, and glycogen deposition in cells.
Article
Pharmacology & Pharmacy
Parisa Badiee, Michelle F. Maritz, Benjamin Thierry
Summary: A nanoformulation of a small molecule GSK3 inhibitor has been developed as a potential alternative to antibody-based checkpoint inhibition. The nanoformulation efficiently inhibits PD-1 expression and improves the survival and proliferation of CAR-T cells, while also increasing the population of memory T cells.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Cell Biology
Tian Xia, Ming Liu, Quan Zhao, Jian Ouyang, Bing Chen, Peipei Xu
Summary: PRMT5 is upregulated in multiple myeloma, and its inhibition enhances cell pyroptosis, while the expression of CASP1 negatively correlated with PRMT5 can be restored by suppressing PRMT5, promoting cell pyroptosis in MM.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Samah Elsaadi, Ida Steiro, Pegah Abdollahi, Esten N. Vandsemb, Rui Yang, Tobias S. Slordahl, Torstein Baade Ro, Eline Menu, Anne-Marit Sponaas, Magne Borset
Summary: The study demonstrates the therapeutic potential of targeting PHGDH in multiple myeloma, suggesting it as a way to overcome resistance to proteasome inhibitors.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2021)
Article
Oncology
Michele Merli, Isacco Ferrarini, Francesco Merli, Alessandro Busca, Roberto Mina, Brunangelo Falini, Riccardo Bruna, Roberto Cairoli, Monia Marchetti, Alessandra Romano, Michele Cavo, Luca Arcaini, Livio Trentin, Chiara Cattaneo, Enrico Derenzini, Nicola Stefano Fracchiolla, Francesco Marchesi, Annamaria Scattolin, Atto Billio, Monica Bocchia, Massimo Massaia, Carlo Gambacorti-Passerini, Francesca Romana Mauro, Massimo Gentile, Sara Mohamed, Matteo Giovanni Della Porta, Elisa Coviello, Daniela Cilloni, Giuseppe Visani, Augusto Bramante Federici, Maria Chiara Tisi, Laura Cudillo, Sara Galimberti, Filippo Gherlinzoni, Livio Pagano, Anna Guidetti, Lorenza Bertu, Paolo Corradini, Francesco Passamonti, Carlo Visco
Summary: A study analyzed data from CLL patients with COVID-19 in Italy and found that male sex, age over 70, recent CLL treatment, and COVID-19 severity were independently associated with poor survival. The study revealed a dismal COVID-related outcome in a significant fraction of CLL patients.
HEMATOLOGICAL ONCOLOGY
(2023)
Article
Hematology
Francesca R. Mauro, Irene Della Starza, Monica Messina, Gianluigi Reda, Livio Trentin, Marta Coscia, Paolo Sportoletti, Lorella Orsucci, Valentina Arena, Gloria Margiotta Casaluci, Roberto Marasca, Roberta Murru, Luca Laurenti, Fiorella Ilariucci, Caterina Stelitano, Donato Mannina, Massimo Massaia, Gian Matteo Rigolin, Lydia Scarfo, Monia Marchetti, Luciano Levato, Monica Tani, Annalisa Arcari, Gerardo Musuraca, Marina Deodato, Piero Galieni, Valeria Belsito Patrizi, Daniela Gottardi, Anna Marina Liberati, Annamaria Giordano, Maria Chiara Molinari, Daniela Pietrasanta, Veronica Mattiello, Andrea Visentin, Candida Vitale, Francesco Albano, Antonino Neri, Lucia Anna De Novi, Maria Stefania De Propris, Mauro Nanni, Ilaria Del Giudice, Anna Guarini, Paola Fazi, Marco Vignetti, Alfonso Piciocchi, Antonio Cuneo, Robin Foa
Summary: The GIMEMA phase II LLC1518 VERITAS trial demonstrated that front-line, fixed-duration venetoclax and rituximab (VenR) combination therapy is highly effective and safe in young, fit patients with chronic lymphocytic leukemia and unfavorable genetic characteristics. The treatment resulted in high rates of complete remission and durable response with undetectable minimal residual disease. No cases of disease progression were observed during the median follow-up of 20.8 months.
Article
Oncology
Alberto Biggi, Stephane Chauvie, Federico Fallanca, Luca Guerra, Fabrizio Bergesio, Massimo Menga, Andrea Bianchi, Michele Gregianin, Agostino Chiaravalloti, Orazio Schillaci, Chiara Pavoni, Caterina Patti, Marco Picardi, Alessandra Romano, Corrado Schiavotto, Roberto Sorasio, Simonetta Viviani, Giorgio La Nasa, Livio Trentin, Alessandro Rambaldi, Andrea Gallamini
Summary: This study demonstrates the accuracy of end-of-treatment FDG-PET/CT in predicting treatment outcome in lymphoma patients, and confirms the appropriateness of the Lugano classification for evaluation.
HEMATOLOGICAL ONCOLOGY
(2023)
Letter
Clinical Neurology
Chiara Briani, Sergio Ferrari, Matteo Tagliapietra, Livio Trentin, Andrea Visentin
JOURNAL OF NEUROLOGY
(2023)
Article
Immunology
Laura Quotti Tubi, Elisa Mandato, Sara Canovas Nunes, Arash Arjomand, Fortunato Zaffino, Sabrina Manni, Alessandro Casellato, Paolo Macaccaro, Nicola Vitulo, Sara Zumerle, Odile Filhol, Brigitte Boldyreff, Christian W. Siebel, Antonella Viola, Giorgio Valle, Federica Mainoldi, Stefano Casola, Valeria Cancila, Alessandro Gulino, Claudio Tripodo, Marco Pizzi, Angelo Paolo Dei Tos, Livio Trentin, Gianpietro Semenzato, Francesco Piazza
Summary: The role of CK2 in B-cell development and activation is not well understood. Using a CK2 beta(KO) mouse model, we found that CK2 beta(KO) mice exhibit increased marginal zone (MZ) B cells and reduced follicular B cells, suggesting a role for CK2 in the regulation of BCR and NOTCH2 signaling pathways. Further analysis revealed enhanced activation of the NOTCH2 pathway in CK2 beta(KO) mice, supporting MZ B-cell development. Additionally, CK2 beta(KO) mice showed alterations in immune response and B-cell activation processes. In vitro assays demonstrated impaired signaling downstream of BCR, Toll-like receptor, CD40, and IL-4R in B cells lacking CK2 beta.
FRONTIERS IN IMMUNOLOGY
(2023)
Letter
Hematology
Ilaria Del Giudice, Luca Vincenzo Cappelli, Julio Delgado, Carsten Utoft Niemann, Michael Asger Andersen, Emelie Hamotal Curovic Rotbain, Kathrine Aarup, Renata Walewska, Andrea Visentin, Marina Deodato, Anna Maria Frustaci, Chiara Cavalloni, Massimo Gentile, Mohamed A. Yassin, Deepesh Lad, Lydia Scarfo, Max Flogegard, Mattias Mattsson, Sara Raponi, Caterina Ilari, Irene Della Starza, Ester M. Orlandi, Alessandra Tedeschi, Livio Trentin, Gianpietro Semenzato, Anna Guarini, Paolo Ghia, Emili Montserrat, Robin Foa
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Letter
Hematology
Francesca R. Mauro, Andrea Visentin, Diana Giannarelli, Maria C. Molinari, Giulia Proietti, Marco Petrella, Francesco Angotzi, Sara Pepe, Livio Trentin, Silvia Baroncelli, Emanuela Giombini, Silvia Meschi, Fabrizio Maggi, Daniele Focosi
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
John N. Allan, Ian W. Flinn, Tanya Siddiqi, Paolo Ghia, Constantine S. Tam, Thomas J. Kipps, Paul M. Barr, Anna Elinder Camburn, Alessandra Tedeschi, Xavier C. Badoux, Ryan Jacobs, Bryone J. Kuss, Livio Trentin, Cathy Zhou, Anita Szoke, Christopher Abbazio, William G. Wierda
Summary: The CAPTIVATE study demonstrates that fixed-duration ibrutinib plus venetoclax is effective in controlling chronic lymphocytic leukemia, including patients with high-risk genomic features. This treatment provides durable progression-free survival and similar overall survival rates.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Francesca R. Mauro, Diana Giannarelli, Clementina M. Galluzzo, Andrea Visentin, Anna M. Frustaci, Paolo Sportoletti, Candida Vitale, Gianluigi Reda, Massimo Gentile, Luciano Levato, Roberta Murru, Daniele Armiento, Maria C. Molinari, Giulia Proietti, Sara Pepe, Filomena De Falco, Veronica Mattiello, Luca Barabino, Roberta Amici, Marta Coscia, Alessandra Tedeschi, Corrado Girmenia, Livio Trentin, Silvia Baroncelli
Summary: This study investigated the COVID-19 morbidity in 200 chronic lymphocytic leukemia (CLL) patients after receiving the SARS-CoV-2 vaccine. The results showed that 41% of patients contracted COVID-19, with 26% requiring hospitalization and 4% dying. Age, prior treatment, and TP53 gene mutation were significantly associated with vaccine response and susceptibility. The study highlights the importance of prevention and mitigation of COVID-19 in CLL patients.
Review
Oncology
Alessandro Cellini, Federico Scarmozzino, Francesco Angotzi, Edoardo Ruggeri, Angelo Paolo Dei Tos, Livio Trentin, Marco Pizzi, Andrea Visentin
Summary: Immune evasion through overexpression of PD-L1 and PD-L2 proteins and the role of the microenvironment are key factors in classical Hodgkin Lymphoma. This review discusses the strategies used by cHL to create an immunosuppressive microenvironment and achieve optimal immune evasion, as well as the success and resistance mechanisms of checkpoint inhibitors in cHL immunotherapy.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Francesco Angotzi, Marco Petrella, Tamara Berno, Gianni Binotto, Giorgia Bonetto, Antonio Branca, Marco Carraro, Chiara Adele Cavaretta, Alessandro Cellini, Fabio D'Amore, Laura Forlani, Ilaria Gianesello, Carmela Gurrieri, Silvia Imbergamo, Federica Lessi, Antonio Maroccia, Federica Mazzetto, Laura Pavan, Sara Pezone, Francesco Piazza, Stefano Pravato, Valeria Ruocco, Greta Scapinello, Fabrizio Vianello, Renato Zambello, Ivan Zatta, Simone Zoletto, Andrea Padoan, Livio Trentin, Andrea Visentin
Summary: The combination of Tixagevimab/Cilgavimab has been approved to decrease symptomatic SARS-CoV-2 infection in high-risk patients. However, its effectiveness in patients with hematological malignancies remains uncertain. This study prospectively evaluated the rate of infection in seronegative patients receiving Tixagevimab/Cilgavimab compared to seropositive patients observed or given a fourth vaccine dose. The findings showed no significant difference in the incidence of infection between the two groups.
FRONTIERS IN ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Nayla Mouawad, Guido Capasso, Edoardo Ruggeri, Leonardo Martinello, Filippo Severin, Andrea Visentin, Monica Facco, Livio Trentin, Federica Frezzato
Summary: The ongoing search for molecules involved in apoptosis resistance and pathogenesis of onco-hematological malignancies has identified Heat Shock Protein of 70kDa (HSP70) as a potential therapeutic target. HSP70, a highly cytoprotective protein, is induced in response to various insults and is associated with poor prognosis and therapy resistance in onco-hematological diseases. This review provides an overview of HSP70's potential as a therapeutic target and explores its partners and inhibitors.
Article
Hematology
Andrea Visentin, Thomas Chatzikonstantinou, Lydia Scarfo, Anargyros Kapetanakis, Christos Demosthenous, Georgios Karakatsoulis
Summary: In this retrospective international multicenter study, the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders infected by SARS-CoV-2 were described. The study also investigated the development of post-COVID condition. The data showed that patients infected in the most recent phases of the pandemic had lower hospitalization rates, ICU admission rates, and mortality compared to those infected in the initial phases. Overall survival improved throughout the phases. Age, comorbidity, and CLL-directed treatment were identified as risk factors for mortality. A significant number of patients developed post-COVID condition, characterized by fatigue, dyspnea, lasting cough, and impaired concentration. The severity of infection was the only risk factor for developing post-COVID. Further investigations are warranted to understand the impact of COVID-19 on CLL patients.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Letter
Hematology
Andrea Visentin, Francesca Romana Mauro, Lydia Scarfo, Massimo Gentile, Lucia Farina, Gianluigi Reda, Isacco Ferrarini, Giulia Proietti, Enrico Derenzini, Francesca Cibien, Candida Vitale, Alessandro Sanna, Daniela Pietrasanta, Monia Marchetti, Roberta Murru, Gian Matteo Rigolin, Paolo Sportoletti, Valentina Trimarco, Chiara Adele Cavarretta, Francesco Angotzi, Alessandro Cellini, Valeria Ruocco, Ivan Zatta, Luca Laurenti, Stefano Molica, Marta Coscia, Paolo Ghia, Robin Foa, Antonio Cuneo, Livio Trentin
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Filippo Severin, Nayla Mouawad, Edoardo Ruggeri, Andrea Visentin, Leonardo Martinello, Elisa Pagnin, Valentina Trimarco, Stefano Pravato, Francesco Angotzi, Monica Facco, Livio Trentin, Federica Frezzato
Summary: Signalling events downstream the B-cell receptor (BCR) are crucial for survival and progression of chronic lymphocytic leukemia (CLL) cells. Focal adhesion kinase (FAK), regulated by calpain, interacts with molecules involved in BCR signalling and disease progression, such as Src/Lyn, cortactin, and HS1. The down-modulation of FAK and its cleavage due to calpain activity were observed upon BCR stimulation. Additionally, FAK inhibitor treatment induced apoptosis in CLL cells, suggesting a potential druggable pathway involving FAK, cortactin, and HS1 in CLL pathogenesis.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)