Article
Immunology
Uri Rozovski, Ivo Veletic, David M. Harris, Ping Li, Zhiming Liu, Preetesh Jain, Taghi Manshouri, Alessandra Ferrajoli, Jan A. Burger, Prithviraj Bose, Phillip A. Thompson, Nitin Jain, William G. Wierda, Srdan Verstovsek, Michael J. Keating, Zeev Estrov
Summary: This study suggests that CLL cells can produce high levels of PTX3, and phosphorylated STAT3 can transcriptionally activate the PTX3 gene. Inhibition of PTX3 may be beneficial for CLL patients.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kristan V. Piroeva, Charlotte Mcdonald, Charalampos Xanthopoulos, Chelsea Fox, Christopher T. Clarkson, Jan-Philipp Mallm, Yevhen Vainshtein, Luminita Ruje, Lara C. Klett, Stephan Stilgenbauer, Daniel Mertens, Efterpi Kostareli, Karsten Rippe, Vladimir B. Teif
Summary: This study compared the nucleosome positions in chronic lymphocytic leukemia (CLL) patients and healthy individuals, and found significant changes in nucleosome positioning in CLL. The spacing between nucleosomes was shortened, and changes in nucleosome occupancy were linked to chromatin remodeling and reduced DNA methylation. Nucleosome positioning can be used to classify CLL subtypes and monitor disease progression.
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
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
Hematology
Stavroula Ntoufa, Marina Gerousi, Stamatia Laidou, Fotis Psomopoulos, Georgios Tsiolas, Theodoros Moysiadis, Nikos Papakonstantinou, Larry Mansouri, Achilles Anagnostopoulos, Niki Stavrogianni, Sarka Pospisilova, Karla Plevova, Antonios M. Makris, Richard Rosenquist, Kostas Stamatopoulos
Summary: Recurrent mutations in the RPS15 gene have been found to rewire the translation program of primary CLL cells, reducing their translational efficiency, with effects not observed in cell lines. Specifically, RPS15 mutations alter the translation efficiency of other ribosomal proteins and regulatory elements, impacting key cellular processes and immune signaling.
Article
Cell Biology
Jennifer C. Reid, Diana Golubeva, Allison L. Boyd, Cameron G. Hollands, Charisa Henly, Luca Orlando, Andrew Leber, Josee Hebert, Fortunato Morabito, Giovanna Cutrona, Luca Agnelli, Massimo Gentile, Manlio Ferrarini, Antonino Neri, Brian Leber, Mickie Bhatia
Summary: Identifying precise targets for individual cancers, particularly chronic lymphocytic leukemia (CLL) with trisomy 12 (tri12), remains challenging. Using tri12 human pluripotent stem cells (hPSCs), specific gene networks and targets were identified and validated, influencing progression-free survival in CLL. Actionable targets were found through drug testing and functional validation, with interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor showing potency and selectivity against tri12 CLL.
Review
Biochemistry & Molecular Biology
Paolo Sportoletti, Filomena De Falco, Beatrice Del Papa, Stefano Baldoni, Valerio Guarente, Andrea Marra, Erica Dorillo, Chiara Rompietti, Francesco Maria Adamo, Loredana Ruggeri, Mauro Di Ianni, Emanuela Rosati
Summary: Key features of CLL include immune system defects and leukemic cells’ ability to evade immune defenses, leading to increased susceptibility to infections and disease progression. The role of NK cells in CLL is less understood, but evidence suggests that NK cell dysfunctions in CLL mainly depend on escape mechanisms employed by leukemic cells. NK cells, with their preserved ADCC function and reversible dysfunctions, are an attractive source for novel immunotherapeutic strategies in CLL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Veronika Ecker, Martina Stumpf, Lisa Brandmeier, Tanja Neumayer, Lisa Pfeuffer, Thomas Engleitner, Ingo Ringshausen, Nina Nelson, Manfred Juecker, Stefan Wanninger, Thorsten Zenz, Clemens Wendtner, Katrin Manske, Katja Steiger, Roland Rad, Markus Mueschen, Juergen Ruland, Maike Buchner
Summary: Current therapeutic approaches in CLL focus on suppressing the PI3K/AKT signaling pathway, but research shows that CLL cells are vulnerable to hyperactivation of this pathway, which may be a promising concept for CLL therapy.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Serena Matis, Anna Grazia Recchia, Monica Colombo, Martina Cardillo, Marina Fabbi, Katia Todoerti, Sabrina Bossio, Sonia Fabris, Valeria Cancila, Rosanna Massara, Daniele Reverberi, Laura Emionite, Michele Cilli, Giannamaria Cerruti, Sandra Salvi, Paola Bet, Simona Pigozzi, Roberto Fiocca, Adalberto Ibatici, Emanuele Angelucci, Massimo Gentile, Paola Monti, Paola Menichini, Gilberto Fronza, Federica Torricelli, Alessia Ciarrocchi, Antonino Neri, Franco Fais, Claudio Tripodo, Fortunato Morabito, Manlio Ferrarini, Giovanna Cutrona
Summary: A specific miRNA (miR-146b-5p) in chronic lymphocytic leukemia (CLL) regulates the expression of IL-12R(31 and the expansion of leukemic cells, thus playing a role in the pathogenesis and treatment of CLL.
Article
Medicine, General & Internal
Han-ying Huang, Yun Wang, Tobias Herold, Robert Peter Gale, Jing-zi Wang, Liang Li, Huan-xin Lin, Yang Liang
Summary: The study found that the expression of immune-related genes in patients with chronic lymphoblastic leukemia can serve as an independent predictor of survival, and the immune risk score (IRS) can predict the survival risk of patients.
FRONTIERS IN MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Brigitte Bauvois, Elodie Pramil, Ludovic Jondreville, Claire Quiney, Florence Nguyen-Khac, Santos A. Susin
Summary: The study reveals that both type I and II interferons promote survival of chronic lymphocytic leukemia cells by activating the STAT3/Mcl-1 signaling pathway, inhibiting intrinsic apoptosis. Inhibitors against STAT3, TYK2 (for type I IFN), JAK2 (for type II IFN), and Src family kinase PP2 can effectively reduce interferon-mediated cell survival. Combining conventional treatments with inhibitors targeting STAT3 and Mcl-1 may offer a new therapeutic strategy for CLL.
Article
Medicine, Research & Experimental
Weimin Kong, Alexander Dimitri, Wenliang Wang, In-Young Jung, Christopher J. Ott, Maria Fasolino, Yan Wang, Irina Kulikovskaya, Minnal Gupta, Todd Yoder, Jamie E. DeNizio, John K. Everett, Erik F. Williams, Jun Xu, John Scholler, Tyler J. Reich, Vijay G. Bhoj, Kathleen M. Haines, Marcela Maus, J. Joseph Melenhorst, Regina M. Young, Julie K. Jadlowsky, Katherine T. Marcucci, James E. Bradner, Bruce L. Levine, David L. Porter, Frederic D. Bushman, Rahul M. Kohli, Carl H. June, Megan M. Davis, Simon F. Lacey, Golnaz Vahedi, Joseph A. Fraietta
Summary: CAR T cell therapy has shown remarkable anti-tumor responses in some B cell malignancies, but there are patients who do not respond due to T cell deficiencies affecting the expansion, persistence, and effector function of CAR T cells. Longitudinal immune profiling identified phenotypic and pharmacodynamic changes in CAR T cells in chronic lymphocytic leukemia patients, revealing that CAR T cell failure may be associated with preexisting T cell defects or acquired dysfunction. Bet epigenetic readers modulation could potentially enhance the efficacy of cell-based immunotherapies.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Immunology
Elisavet Vlachonikola, Kostas Stamatopoulos, Anastasia Chatzidimitriou
Summary: Chronic lymphocytic leukemia remains incurable despite recent progress in management, highlighting the importance of further investigating the underlying pathophysiology. The interactions between malignant CLL cells and the tumor microenvironment play a crucial role in disease progression, with T cell abnormalities and potential therapeutic targets being a key focus in enhancing targeted cytotoxic activity against the malignant clone.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Dana Ghergus, Mickael Martin, Anne-Marie Knapp, Fabien Delmotte, Aurelie Joublin-Delavat, Sophie Jung, Jean-Nicolas Schickel, Isabelle Mendel, Arnaud Dupuis, Bernard Drenou, Herve Ghesquieres, Gilles Salles, Lucile Baseggio, Raoul Herbrecht, Anne-Sophie Korganow, Laurent Vallat, Pauline Soulas-Sprauel, Eric Meffre, Thierry Martin
Summary: This study found that ZAP70 is expressed in nonmalignant B cells in CLL patients and is associated with autoimmune cytopenia. This finding contributes to a better understanding of the role of ZAP70 in CLL leukemogenesis and the mechanisms of autoimmune complications.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Medicine, General & Internal
Barbara Eichhorst, Carsten U. Niemann, Arnon P. Kater, Moritz Fuerstenau, Julia von Tresckow, Can Zhang, Sandra Robrecht, Michael Gregor, Gunnar Juliusson, Patrick Thornton, Philipp B. Staber, Tamar Tadmor, Vesa Lindstrom, Caspar da Cunha-Bang, Christof Schneider, Christian B. Poulsen, Thomas Illmer, Bjoern Schoettker, Thomas Noesslinger, Ann Janssens, Ilse Christiansen, Michael Baumann, Henrik Frederiksen, Marjolein van der Klift, Ulrich Jaeger, Maria B. L. Leys, Mels Hoogendoorn, Kourosh Lotfi, Holger Hebart, Tobias Gaska, Harry Koene, Lisbeth Enggaard, Jereon Goede, Josien C. Regelink, Anouk Widmer, Florian Simon, Nisha De Silva, Anna-Maria Fink, Jasmin Bahlo, Kirsten Fischer, Clemens-Martin Wendtner, Karl A. Kreuzer, Matthias Ritgen, Monika Brueggemann, Eugen Tausch, Mark-David Levin, Marinus van Oers, Christian Geisler, Stephan Stilgenbauer, Michael Hallek
Summary: In fit patients with CLL, venetoclax-obinutuzumab, with or without ibrutinib, showed superior results compared to chemoimmunotherapy as a first-line treatment, with higher rates of undetectable minimal residual disease and progression-free survival.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)