Article
Immunology
Begum Alankus, Veronika Ecker, Nathalie Vahl, Martina Braun, Wilko Weichert, Stephan Macher-Goeppinger, Torben Gehring, Tanja Neumayer, Thorsten Zenz, Maike Buchner, Juergen Ruland
Summary: This study revealed that aberrant B cell-intrinsic RANK signaling may drive autoimmunity and B cell malignancy, and inhibition of the RANKL-RANK axis can kill CLL cells.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Hematology
Freda K. Stevenson, Francesco Forconi, Thomas J. Kipps
Summary: Research into chronic lymphocytic leukemia has led to significant improvements in the assessment and treatment of patients, with designer drugs now successfully targeting tumor cells based on their biology. Classifying CLL into unmutated (U) and mutated (M) diseases based on the mutational status of IGHV sequences reveals distinct origins, biology, and clinical behaviors for each. Despite advances, challenges such as cell-escape strategies and immunosuppression remain, necessitating continued research into CLL biology.
Article
Cell Biology
Damjan Avsec, Marja Skrlj Miklavcic, Tilen Burnik, Masa Kanduser, Marusa Bizjak, Helena Podgornik, Irena Mlinaric-Rascan
Summary: Chronic lymphocytic leukemia (CLL) is a type of hematological cancer involving B lymphocytes, and venetoclax is a commonly used targeted therapy. This study found that certain molecular mechanisms in CLL cells can lead to resistance to venetoclax, but targeting these mechanisms can overcome the resistance.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Alicia M. Vaca, Nikolaos Ioannou, Mariela Sivina, Elisavet Vlachonikola, Karen Clise-Dwyer, Ekaterina Kim, Dan Li, Qing Ma, Alessandra Ferrajoli, Zeev Estrov, William G. Wierda, Piers E. M. Patten, Alan G. Ramsay, Jan A. Burger
Summary: This study reveals the interaction and clonal expansion mechanism between chronic lymphocytic leukemia (CLL) cells and T-cell subsets, indicating the interaction of Tfh cells with proliferating leukemia cells and providing new avenues for treating CLL.
Article
Hematology
Fabienne Meier-Abt, Junyan Lu, Ester Cannizzaro, Marcel F. Pohly, Sandra Kummer, Sibylle Pfammatter, Laura Kunz, Ben C. Collins, Ferran Nadeu, Kwang Seok Lee, Peng Xue, Myriam Gwerder, Michael Roiss, Jennifer Huellein, Sebastian Scheinost, Sascha Dietrich, Elias Campo, Wolfgang Huber, Ruedi Aebersold, Thorsten Zenz
Summary: This study uncovered mutations affecting protein expression in CLL and identified signaling pathways associated with trisomy 12. STAT2 protein expression was linked to specific drug responses, providing a protein expression reference map for CLL.
Article
Biochemistry & Molecular Biology
Alejandro M. Hortal, Clara L. Oeste, Claudia Cifuentes, Miguel Alcoceba, Isabel Fernandez-Pisonero, Laura Clavain, Rut Tercero, Pilar Mendoza, Veronica Dominguez, Marta Garcia-Flores, Belen Pintado, David Abia, Carmen Garcia-Macias, Almudena Navarro-Bailon, Xose R. Bustelo, Marcos Gonzalez, Balbino Alarcon
Summary: The overexpression of wild type RRAS2 is found to be associated with the development of CLL. A single nucleotide polymorphism (rs8570) in the 3'UTR of RRAS2 mRNA is linked to higher expression of RRAS2 and more aggressive disease in CLL. Overexpression of wild type RRAS2 in mice provokes the development of CLL, accompanied by strong convergent selection of somatic mutations. The R-RAS2 protein physically binds to the BCR and mediates BCR signals in CLL.
Article
Biochemistry & Molecular Biology
Audrey L. Smith, Alexandria P. Eiken, Sydney A. Skupa, Dalia Y. Moore, Lelisse T. Umeta, Lynette M. Smith, Elizabeth R. Lyden, Christopher R. D'Angelo, Avyakta Kallam, Julie M. Vose, Tatiana G. Kutateladze, Dalia El-Gamal
Summary: This study demonstrates the preclinical efficacy of SRX3305, a novel inhibitor, in chronic lymphocytic leukemia (CLL). SRX3305 can target multiple disease-driving factors in CLL, inhibiting cell proliferation and migration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Natasha Malik, Jodie Hay, Hassan N. B. Almuhanna, Karen M. Dunn, Jamie Lees, Jennifer Cassels, Jiatian Li, Rinako Nakagawa, Owen J. Sansom, Alison M. Michie
Summary: This study reveals the essential role of mTORC1 in the initiation/maintenance of leukemia in a CLL model and identifies the inactivation of eEF2 activity as a novel therapeutic target for blocking CLL progression.
Article
Oncology
Marina Gerousi, Fotis Psomopoulos, Konstantia Kotta, Maria Tsagiopoulou, Niki Stavroyianni, Achilles Anagnostopoulos, Athanasios Anastasiadis, Maria Gkanidou, Ioannis Kotsianidis, Stavroula Ntoufa, Kostas Stamatopoulos
Summary: The study found that the calcitriol/VDR system is functional in CLL, regulating key signaling pathways for cell survival and proliferation. Microenvironmental signals can modulate VDR expression and function, but calcitriol acts independently, suggesting a potential clinical utility of vitamin D supplementation in CLL patients.
Article
Immunology
Francesca Vittoria Sbrana, Riccardo Pinos, Federica Barbaglio, Davide Ribezzi, Fiorella Scagnoli, Lydia Scarfo, Itedale Namro Redwan, Hector Martinez, Silvia Fare, Paolo Ghia, Cristina Scielzo
Summary: The study introduced the use of three-dimensional bioprinting technology to establish an in vitro model of Chronic Lymphocytic Leukemia (CLL), successfully increasing cell viability in vitro and establishing a long-term 3D culture model. Through RNA sequencing analysis, consistent differences in gene expression profiles between 2D and 3D samples were observed, indicating the potential of this new model to better mimic physiological conditions for cell interactions in vivo.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Emma Kennedy, Eve Coulter, Emma Halliwell, Nuria Profitos-Peleja, Elisabeth Walsby, Barnaby Clark, Elizabeth H. Phillips, Thomas A. Burley, Simon Mitchell, Stephen Devereux, Christopher D. Fegan, Christopher Jones, Rosalynd Johnston, Tim Chevassut, Ralph Schulz, Martina Seiffert, Angelo Agathanggelou, Ceri Oldreive, Nicholas Davies, Tatjana Stankovic, Triantafillos Liloglou, Chris Pepper, Andrea G. S. Pepper
Summary: Despite the advancements in B-cell receptor-targeted inhibitors, CLL remains incurable. TLR9 activation by unmethylated DNA is associated with disease progression in CLL. High TLR9 expression promotes CLL cell migration and disease progression, while dual targeting of TLR9 and BTK shows strong synergism as a potential treatment strategy for this incurable disease.
Review
Oncology
Ilenia Sana, Maria Elena Mantione, Piera Angelillo, Marta Muzio
Summary: In recent years, significant progress has been made in the clinical management of chronic lymphocytic leukemia and other B-cell malignancies by targeting B-cell receptor signaling molecules. However, a proportion of patients remain uncured, leading to efforts in studying new potential targets. NFAT is overexpressed and constitutively activated in CLL, with targeting this molecule impacting on CLL cell viability.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Serena Matis, Martina Rossi, Lorenzo Brondolo, Martina Cardillo, Daniele Reverberi, Rosanna Massara, Monica Colombo, Adalberto Ibatici, Emanuele Angelucci, Tiziana Vaisitti, Silvia Bruno, Sonia Fabris, Antonino Neri, Massimo Gentile, Fortunato Morabito, Giovanna Cutrona, Paola Briata, Roberto Gherzi, Franco Fais
Summary: Long non-coding RNA LINC00152 expression is regulated by immunomodulatory signals in normal B cells, but its role in Chronic Lymphocytic Leukemia (CLL) cells is less effective. Despite variable expression in CLL patients, LINC00152 does not appear to contribute significantly to CLL cell expansion or survival.
HEMATOLOGICAL ONCOLOGY
(2022)
Article
Oncology
Cedric Schleiss, Raphael Carapito, Luc-Matthieu Fornecker, Leslie Muller, Nicodeme Paul, Ouria Tahar, Angelique Pichot, Manuela Tavian, Alina Nicolae, Laurent Miguet, Laurent Mauvieux, Raoul Herbrecht, Sarah Cianferani, Jean-Noel Freund, Christine Carapito, Myriam Maumy-Bertrand, Seiamak Bahram, Frederic Bertrand, Laurent Vallat
Summary: The study reveals a proliferative genetic program activated by BCR in primary leukemic cells, consisting of 430 genes and 374 proteins. Mathematical modeling highlights a transcriptional network associated with cell proliferation.
Article
Oncology
Michael Asger Andersen, Klaus Rostgaard, Carsten Utoft Niemann, Henrik Hjalgrim
Summary: The study found that CLL patients have increased susceptibility to infections for decades before diagnosis, and a similar pattern was observed in the offspring of CLL patients. The duration of this time window is consistent with immune dysfunction and/or certain infections playing a causal role in CLL pathogenesis, potentially mediating the association between constitutional infection susceptibility and CLL risk.
Editorial Material
Hematology
Joseph R. Slupsky
Article
Immunology
Kathleen J. Till, Andrew R. Pettitt, Joseph R. Slupsky
JOURNAL OF IMMUNOLOGY
(2015)
Article
Oncology
Wafa Abu-Alainin, Thompson Gana, Triantafillos Liloglou, Adedamola Olayanju, Lawrence N. Barrera, Robert Ferguson, Fiona Campbell, Timothy Andrews, Christopher Goldring, Neil Kitteringham, Brian K. Park, Taoufik Nedjadi, Michael C. Schmid, Joseph R. Slupsky, William Greenhalf, John P. Neoptolemos, Eithne Costello
JOURNAL OF PATHOLOGY
(2016)
Article
Multidisciplinary Sciences
Mosavar Farahani, Carlos Rubbi, Luning Liu, Joseph R. Slupsky, Nagesh Kalakonda
Article
Multidisciplinary Sciences
Ola Al-Sanabra, Andrew D. Duckworth, Mark A. Glenn, Benjamin R. B. Brown, Piera Angelillo, Kelvin Lee, John Herbert, Francesco Falciani, Nagesh Kalakonda, Joseph R. Slupsky
SCIENTIFIC REPORTS
(2017)
Article
Multidisciplinary Sciences
Kathleen J. Till, John C. Allen, Fatima Talab, Ke Lin, David Allsup, Lynn Cawkwell, Alison Bentley, Ingo Ringshausen, Andrew D. Duckworth, Andrew R. Pettitt, Nagesh Kalakonda, Joseph R. Slupsky
SCIENTIFIC REPORTS
(2017)
Article
Biochemical Research Methods
Andrew D. Duckworth, Pier Federico Gherardini, Martina Sykorova, Faten Yasin, Garry P. Nolan, Joseph R. Slupsky, Nagesh Kalakonda
Editorial Material
Hematology
Joseph R. Slupsky
Article
Oncology
Carlos R. Figueiredo, Helen Kalirai, Joseph J. Sacco, Ricardo A. Azevedo, Andrew Duckworth, Joseph R. Slupsky, Judy M. Coulson, Sarah E. Coupland
JOURNAL OF PATHOLOGY
(2020)
Article
Multidisciplinary Sciences
Ali A. Azar, Alison M. Michie, Anuradha Tarafdar, Natasha Malik, Geetha K. Menon, Kathleen J. Till, Nikolina Vlatkovic, Joseph R. Slupsky
SCIENTIFIC REPORTS
(2020)
Article
Oncology
Adam J. Linley, Laura Karydis, Anil K. Mondru, Annalisa D'Avola, Humood Al Shmrany, Silvia Cicconi, Rebecca Griffin, Francesco Forconi, Andrew R. Pettitt, Nagesh Kalakonda, Andrew C. Rawstron, Peter Hillmen, Andrew J. Steele, David J. MacEwan, Graham Packham, Ian A. Prior, Joseph R. Slupsky
Summary: This study employed a high-resolution approach to investigate the impact of BCR signaling in CLL cells, revealing patient-specific kinase signatures and adaptive signaling reprogramming. This provides new insights into the effects of therapy on signaling response.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Jodie Hay, Anuradha Tarafdar, Ailsa K. Holroyd, Hothri A. Moka, Karen M. Dunn, Alzahra Alshayeb, Bryony H. Lloyd, Jennifer Cassels, Natasha Malik, Ashfia F. Khan, IengFong Sou, Jamie Lees, Hassan N. B. Almuhanna, Nagesh Kalakonda, Joseph R. Slupsky, Alison M. Michie
Summary: The expression of PKC beta facilitates leukemogenesis in chronic lymphocytic leukemia (CLL) and BCR-mediated signaling is identified as a key driver of CLL development in the PKC alpha-KR model.
Correction
Hematology
J. R. Slupsky
Review
Oncology
Leah J. Wilson, Adam Linley, Dean E. Hammond, Fiona E. Hood, Judy M. Coulson, David J. MacEwan, Sarah J. Ross, Joseph R. Slupsky, Paul D. Smith, Patrick A. Eyers, Ian A. Prior
Article
Oncology
Stephen Middle, Sarah E. Coupland, Azzam Taktak, Victoria Kidgell, Joseph R. Slupsky, Andrew R. Pettitt, Kathleen J. Till
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2015)