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
Clare Sun, Chen Yun-Ching, Aina Martinez Zurita, Maria Joao Baptista, Stefania Pittaluga, Delong Liu, Daniel Rosebrock, Satyen Harish Gohil, Nakhle S. Saba, Theresa Davies-Hill, Sarah E. M. Herman, Gad Getz, Mehdi Pirooznia, Catherine J. Wu, Adrian Wiestner
Summary: In CLL, oncogenic processes are upregulated in the lymph nodes and in cases with unmutated IGHV region. Single-cell RNA sequencing reveals 3 major cell states in CLL: quiescent, activated, and proliferating. Activated tumor cells are associated with inferior treatment-free survival and the presence of activated CD4+ memory T cells and M2 macrophages in the lymph nodes. Clonal evolution occurs in approximately half of the patients, but is not associated with AICDA expression. However, a T-cell inflamed microenvironment in the lymph nodes is associated with clonal stability.
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.
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
Multidisciplinary Sciences
Elena Cesaro, Andrea Patrizia Falanga, Rosa Catapano, Francesca Greco, Simona Romano, Nicola Borbone, Arianna Pastore, Maria Marzano, Federico Chiurazzi, Stefano D'Errico, Gennaro Piccialli, Giorgia Oliviero, Paola Costanzo, Michela Grosso
Summary: In this study, we successfully downregulated the expression of CD5 in chronic lymphocytic leukemia using an innovative antisense approach based on Peptide Nucleic Acids. The results suggest that anti-CD5 PNAs could be potential therapeutics for CLL.
Article
Oncology
Iria Fernandez Botana, Giulia Pagano, Etienne Moussay, Jerome Paggetti
Summary: Chronic lymphocytic leukemia is the most common adult leukemia in the western world, and its interactions with the surrounding immune landscape are crucial for therapeutic interventions. Recent research has shown that the cytokine IL-27 exerts a strong anti-tumor role in CLL through a T-cell mediated mechanism.
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.
Review
Medicine, General & Internal
Mazyar Shadman
Summary: Chronic lymphocytic leukemia is an immunocompromised blood cancer that can be treated with targeted agents like BTK inhibitors or BCL2 inhibitors, but currently there is no cure for the disease.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
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)
Review
Oncology
Elisavet Vlachonikola, Kostas Stamatopoulos, Anastasia Chatzidimitriou
Summary: The treatment of chronic lymphocytic leukemia (CLL) is continuously evolving, with immunotherapy emerging as a therapeutic option to boost immune responses against tumors. However, not all patients benefit from this approach, partly due to dysfunctional T cells in CLL. The tumor microenvironment (TME) is also crucial in impacting immune responses and tumor growth, highlighting the importance of understanding T cell defects and finding ways to overcome them for effective immunotherapy in CLL.
Article
Immunology
Heng-Mo Rong, Han-Yu-Jie Kang, Zhao-Hui Tong
Summary: This study aimed to investigate the metabolic changes in Pneumocystis infection and the metabolic abnormalities in BAFF-R-deficient mice with Pneumocystis infection. The results showed that many metabolites, mainly lipids and lipid-like molecules, were dysregulated in Pneumocystis-infected mice. In addition, B-cell development and function might be associated with lipid metabolism. Conclusion: Metabolism plays a vital role in the immune response to Pneumocystis infection.
JOURNAL OF INFLAMMATION RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Veronika Mancikova, Michal Smida
Summary: CAR T-cell therapy has shown remarkable remissions in difficult-to-treat patients with B-cell malignancies, but the efficacy in chronic lymphocytic leukemia patients is the lowest among B-cell tumors, requiring further investigation into treatment mechanisms and failure reasons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Piers E. M. Patten, Gerardo Ferrer, Shih-Shih Chen, Jonathan E. Kolitz, Kanti R. Rai, Steven L. Allen, Jacqueline C. Barrientos, Nikolaos Ioannou, Alan G. Ramsay, Nicholas Chiorazzi
Summary: The patient-derived xenograft models of chronic lymphocytic leukemia (CLL) can be established using highly immunodeficient animals, allowing the analysis of primary tumor cells in vivo. By pre-activating CLL-derived T lymphocytes in vitro, a reliable system for primary CLL cell growth within a fully autologous system can be achieved. The growth kinetics and degree of anatomic localization of CLL B and T cells are significantly influenced by the route of administration, with different patterns observed between intravenous and intraperitoneal delivery. This model provides a powerful tool for evaluating CLL biology and novel therapeutics in vivo.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Francesca Perutelli, Rebecca Jones, Valentina Griggio, Candida Vitale, Marta Coscia
Summary: Immune-based therapeutic strategies have revolutionized the treatment of hematological disorders by enhancing the immune response against tumor cells. However, individual use of immunotherapy has not shown optimal results in terms of disease control due to CLL-related immune dysfunctions. The understanding of the interactions between immune cells and tumor cells has led to the development of novel combination approaches that hold promise for future treatment of CLL.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Maria Cristina Puzzolo, Ilaria Del Giudice, Nadia Peragine, Paola Mariglia, Maria Stefania De Propris, Luca Vincenzo Cappelli, Livio Trentin, Gianluigi Reda, Antonio Cuneo, Stefano Molica, Alfonso Piciocchi, Valentina Arena, Francesca Romana Mauro, Anna Guarini, Robin Foa
Summary: Research suggests that ibrutinib treatment can reverse T-cell polarization in chronic lymphocytic leukemia (CLL), decreasing Th2 cells and increasing Th1 cells, with a gradual reduction in the Th2/Th1 ratio after treatment initiation. Furthermore, patients with a Th2/Th1 ratio below 0.088 at M8 are more likely to achieve complete remission (CR).
FRONTIERS IN ONCOLOGY
(2021)
Article
Immunology
Cristiane J. Nunes-Santos, Hye Sun Kuehn, Sergio D. Rosenzweig
Summary: The study evaluated the in vitro activity of the FDA-approved alpha-glucosidase inhibitor against SARS-CoV-2 and its effects on glycoprotein modifications in an overexpression system. Despite clear N-glycan alteration induced by miglustat, the functions of the studied Covid-19-related glycoproteins were not affected, indicating that miglustat is unlikely to alter the natural course of the disease.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
Review
Immunology
Hye Sun Kuehn, Cristiane J. Nunes-Santos, Sergio D. Rosenzweig
Summary: IKAROS, encoded by IKZF1, is a crucial regulator of hematopoiesis and its mutations are associated with immune deficiency, autoimmunity, and malignancy. Loss-of-function mutations in IKZF1 increase the susceptibility to B cell acute lymphoblastic leukemia (B-ALL), while germline heterozygous IKZF1 mutations are linked to immune deficiency and hematologic phenotypes.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
Article
Immunology
Brigette Boast, Lisa A. Miosge, Hye Sun Kuehn, Vicky Cho, Vicki Athanasopoulos, Hayley A. McNamara, Yovina Sontani, Yan Mei, Debbie Howard, Henry J. Sutton, Sofia A. Omari, Zhijia Yu, Mariam Nasreen, T. Daniel Andrews, Ian A. Cockburn, Christopher C. Goodnow, Sergio D. Rosenzweig, Anselm Enders
Summary: IKZF1 is crucial for normal lymphopoiesis, with an L132P mutation leading to B cell-specific phenotype and partial immunodeficiency, shedding light on the development and function of the immune system.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Allergy
Cristiane J. Nunes-Santos, Christopher Koh, Anjali Rai, Keith Sacco, Beatriz E. Marciano, David E. Kleiner, Jamie Marko, Jenna R. E. Bergerson, Michael Stack, Maria M. Rivera, Gregory Constantine, Warren Strober, Gulbu Uzel, Ivan J. Fuss, Luigi D. Notarangelo, Steven M. Holland, Sergio D. Rosenzweig, Theo Heller
Summary: This study describes the prevalence, associated features, and impact of nodular regenerative hyperplasia (NRH) in patients with X-linked agammaglobulinemia (XLA). The results show that NRH is a frequent and severe complication in XLA, associated with increased morbidity, mortality, and liver dysfunction.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Motoi Yamashita, Hye Sun Kuehn, Kazuki Okuyama, Satoshi Okada, Yuzaburo Inoue, Noriko Mitsuiki, Kohsuke Imai, Masatoshi Takagi, Hirokazu Kanegane, Masahiro Takeuchi, Naoki Shimojo, Miyuki Tsumura, Aditya K. Padhi, Kam Y. J. Zhang, Bertrand Boisson, Jean-Laurent Casanova, Osamu Ohara, Sergio D. Rosenzweig, Ichiro Taniuchi, Tomohiro Morio
Summary: The study reveals a human-inherited adaptive immunity disorder mainly characterized by B cell differentiation defect caused by a heterozygous missense variant in IKZF3, resulting in a glycine-to-arginine replacement in the DNA-binding domain of the AIOLOS protein. The mutant AIOLOS protein leads to impaired protein function by forming heterodimers that interfere with wild-type AIOLOS and IKAROS, preventing normal gene expression.
Letter
Allergy
Muhammad Bilal Khalid, Sonia Gaspar Lemos, Katherine Myint-Hpu, Debbie Draper, Jennifer Stoddard, Julie E. Niemela, Sergio D. Rosenzweig, Stefania Pittaluga, Ottavia M. Delmonte, Luigi D. Notarangelo
PEDIATRIC ALLERGY AND IMMUNOLOGY
(2022)
Review
Pediatrics
Brigette Boast, Cristiane De Jesus Nunes-Santos, Hye Sun Kuehn, Sergio D. Rosenzweig
Summary: The normal expression of Ikaros (IKZF1) is crucial for proper functioning of the immune system in both humans and mice. Mutations in IKZF1 have different clinical outcomes in patients, including immunodeficiency, immune dysregulation, and cancer. Studies in mice and humans have provided insights into the biological role of IKZF1 in the immune system and its impact on disease.
FRONTIERS IN PEDIATRICS
(2021)
Review
Immunology
Motoi Yamashita, Tomohiro Morio
Summary: IKAROS is a pioneer protein in the IKZF family of transcription factors, playing a crucial role in lymphocyte development. Inborn errors of IKAROS have been found in patients with B cell deficiency and hypogammaglobulinemia, leading to recurrent sinopulmonary infections, autoimmunity, and hematologic malignancies. Missense mutations involving asparagine at the 159th position can result in combined immunodeficiency. Other transcription factors like AIOLOS, HELIOS, and PEGASUS have also been associated with B cell deficiency, Evans syndrome, and hereditary thrombocytopenia, respectively.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Editorial Material
Immunology
Kazuki Okuyama, Ichiro Taniuchi
Summary: Thpok, a member of the BTB-ZF transcription factor family, is unique in repressing cytotoxic lineage-related genes by recruiting the NuRD chromatin-remodeling complex, as revealed by the related research article by Gao et al.
SCIENCE IMMUNOLOGY
(2022)
Article
Immunology
Keith Sacco, Hye Sun Kuehn, Tomoki Kawai, Nouf Alsaati, Lauren Smith, Blachy Davila, Vanessa Bundy, Douglas B. Kuhns, Kerry Dobbs, Ottavia Delmonte, Luigi D. Notarangelo, Sergio D. Rosenzweig, Michael D. Keller
Summary: This study describes a rare case of autoimmunity and autoinflammation caused by a heterozygous gain-of-function variant in the IKBKB gene. The variant is associated with impaired cell degradation and increased macrophage activation, providing important insights into a novel clinical phenotype.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Editorial Material
Oncology
Motoi Yamashita, Masae Kuroha, Yuko Kinowawki, Nao Kashiwagi, Kotaro Watanabe, Mika Nagase, Daiki Niizato, Noriko Mitsuiki, Takeshi Isoda, Takahiro Kamiya, Atsuko Arisaka, Motoki Inaji, Kenichi Ohashi, Kohsuke Imai, Hirokazu Kanegane, Tomohiro Morio, Masatoshi Takagi
PEDIATRIC BLOOD & CANCER
(2023)
Article
Multidisciplinary Sciences
Cristiane J. Nunes-Santos, HyeSun Kuehn, Brigette Boast, SuJin Hwang, Douglas B. Kuhns, Jennifer Stoddard, Julie E. Niemela, Danielle L. Fink, Stefania Pittaluga, Mones Abu-Asab, John S. Davies, Valarie A. Barr, Tomoki Kawai, Ottavia M. Delmonte, Marita Bosticardo, Mary Garofalo, Magda Carneiro-Sampaio, Raz Somech, Mohammad Gharagozlou, Nima Parvaneh, Lawrence E. Samelson, Thomas A. Fleisher, Anne Puel, Luigi D. Notarangelo, Bertrand Boisson, Jean-Laurent Casanova, Beata Derfalvi, Sergio D. Rosenzweig
Summary: This study describes the first cases of germline biallelic null mutations in ARPC5, a subunit of the Arp2/3 actin nucleator complex. These mutations disrupt actin function and cytokine signaling, causing a range of symptoms including infections, autoimmunity, inflammation, and dysmorphisms. Additionally, the study demonstrates the distinctive impact of this syndrome on interleukin-6 (IL-6) signaling.
NATURE COMMUNICATIONS
(2023)