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.
Review
Oncology
Kristyna Zavacka, Karla Plevova
Summary: Chromothripsis, a mechanism of massive chromosome shattering and reassembly, has been observed in various cancer types, particularly in chronic lymphocytic leukemia (CLL), where it has significant impact on the disease pathology. Recent studies suggest that chromothripsis may be more common than initially thought, especially in CLL cases with adverse clinical outcomes.
FRONTIERS IN ONCOLOGY
(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
Immunology
Giovanna Merchand-Reyes, Ramasamy Santhanam, Frank H. Robledo-Avila, Christoph Weigel, Juan De Dios Ruiz-Rosado, Xiaokui Mo, Santiago Partida-Sanchez, Jennifer A. Woyach, Christopher C. Oakes, Susheela Tridandapani, Jonathan P. Butchar
Summary: The development of nurse-like cells (NLCs) in chronic lymphocytic leukemia (CLL) depends on MEK signaling, and inhibition of MEK can slow down CLL progression and increase survival time in vivo. Targeting the MEK/ERK pathway may be an effective treatment strategy for CLL.
JOURNAL OF IMMUNOLOGY
(2022)
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
Oncology
Paolo Giannoni, Cecilia Marini, Giovanna Cutrona, Gian Mario Sambuceti, Franco Fais, Daniela de Totero
Summary: Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. In this disease, interactions between CLL cells and bone tissue components may lead to alterations in bone homeostasis. Recent research suggests that disruption of the endosteal niche by the expansion of a leukemic B cell clone is worth further investigation for potential therapeutic approaches.
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.
Review
Hematology
Rebecka Svanberg, Sine Janum, Piers E. M. Patten, Alan G. Ramsay, Carsten U. Niemann
Summary: The tumor microenvironment plays a crucial role in the development and survival of malignant B-cell clones in chronic lymphocytic leukemia. Therapeutic strategies targeting the interactions within the microenvironment may significantly impact clinical efficacy. Understanding the effects of current therapeutic agents on microenvironmental cells and interactions can guide and improve CLL treatment strategies.
Review
Oncology
Zong-Han Wang, Wei Li, Hao Dong, Fujun Han
Summary: Chronic lymphocytic leukemia (CLL) is a common hematological disease with a high incidence in western countries. Conventional chemotherapy and targeted therapeutic drugs have limitations in high-risk patients. Immunotherapy, particularly using natural killer (NK) cells, has shown potential for improved prognosis. NK cells enhance immune response through various mechanisms, including antibody-dependent cytotoxicity (ADCC), allogeneic NK cell therapy, and CAR-NK cell therapy. This article reviews the characteristics of NK cells, their receptors, and the advantages and disadvantages of NK cell-based immunotherapies for CLL.
FRONTIERS IN ONCOLOGY
(2023)
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.
Review
Hematology
Sigrid S. Skanland, Anthony R. Mato
Summary: Insight into the mechanisms of resistance to targeted therapies in chronic lymphocytic leukemia (CLL) has led to the development of strategies to prevent and overcome resistance, including combination therapies targeting bypass mechanisms, temporally sequencing of therapies, improved clinical trial designs, and real-time monitoring of patient response. These approaches aim to secure effective treatment options at the relapsed setting and overcome acquired resistance to existing therapies.
Review
Immunology
Yanyan Liu, Yongping Song, Qingsong Yin
Summary: This review summarizes the effects of ibrutinib on the tumor microenvironment and cellular immunity in patients with CLL, particularly focusing on the behavior and function of T cells. The potential mechanisms of ibrutinib are explored, providing a basis for the clinical benefits of long-term ibrutinib treatment and combined therapy based on T-cell-based immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Laura Patrussi, Nagaja Capitani, Cosima T. Baldari
Summary: IL-9, a soluble factor secreted by immune cells, has been found in several tumor niches, with dual roles in promoting or counteracting tumor development depending on the specific type of cancer. Recent studies implicate IL-9 in chronic lymphocytic leukemia pathogenesis, yet the molecular mechanisms remain unclear.
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.
Meeting Abstract
Hematology
Jacqueline R. Rivas, Sara S. Alhakeem, Joseph M. Eckenrode, Yinan Zhang, James P. Collard, Gerhard C. Hildebrandt, Roger A. Fleischman, Li Chen, Jon S. Thorson, Markos Leggas, Subbarao Bondada
Article
Cardiac & Cardiovascular Systems
Gopalkrishna Sreejit, Ahmed Abdel-Latif, Baskaran Athmanathan, Rahul Annabathula, Ashish Dhyani, Sunil K. Noothi, Gregory A. Quaife-Ryan, Annas Al-Sharea, Gerard Pernes, Dragana Dragoljevic, Hind Lal, Kate Schroder, Beatriz Y. Hanaoka, Chander Raman, Maria B. Grant, James E. Hudson, Susan S. Smyth, Enzo R. Porrello, Andrew J. Murphy, Prabhakara R. Nagareddy
Article
Cell Biology
Bright Asare-Bediako, Sunil K. Noothi, Sergio Li Calzi, Baskaran Athmanathan, Cristiano P. Vieira, Yvonne Adu-Agyeiwaah, Mariana Dupont, Bryce A. Jones, Xiaoxin X. Wang, Dibyendu Chakraborty, Moshe Levi, Prabhakara R. Nagareddy, Maria B. Grant
Review
Oncology
Mary K. McKenna, Amanda Rosewell-Shaw, Masataka Suzuki
Review
Chemistry, Medicinal
Harbinder Singh, Vikrant Rai, Sunil K. Nooti, Devendra K. Agrawal
Summary: There has been significant progress in the discovery of novel ligands and modulators of TREMs in the last five years that mainly revolved around the function of TREM molecules. A few peptides showed encouraging results to modulate the expression and activity of TREMs in preclinical studies, and these peptides are currently under clinical investigation. Based on the findings so far in several careful studies, we expect novel therapeutics in the near future which could have the ability to treat various disease conditions associated with TREM expression.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2021)
Article
Oncology
J. R. Rivas, Y. Liu, S. S. Alhakeem, J. M. Eckenrode, F. Marti, J. P. Collard, Y. Zhang, K. A. Shaaban, N. Muthusamy, G. C. Hildebrandt, R. A. Fleischman, L. Chen, J. S. Thorson, M. Leggas, S. Bondada
Summary: In CLL, T-cell dysfunction is driven by molecules like PD-L1 and IL-10. Suppressing IL-10 using a novel inhibitor enhances antitumor T-cell activity and responses to ICB. Targeting IL-10 provides a novel strategy to improve immunotherapies in CLL patients who do not respond well to current therapies.
Review
Immunology
Joseph Greene, Ben F. Brian Iv, S. Erandika Senevirathne, Tanya Freedman
Summary: Myeloid cells play a crucial role in surveilling the body for infection and damage, regulating tissue homeostasis, and initiating immune responses. Their activation is tightly regulated to balance immune protection and tissue preservation.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Article
Cell & Tissue Engineering
Pinar Ataca Atilla, Mary K. McKenna, Norihiro Watanabe, Maksim Mamonkin, Malcolm K. Brenner, Erden Atilla
Summary: This study demonstrates that combinatorial targeting of CD33 or CD123 and CLL-1 using CAR T cells can effectively control the growth of heterogeneous AML tumors and improve survival rates.
Article
Oncology
James P. Collard, Mary K. McKenna, Sunil K. Noothi, Sara S. Alhakeem, Jacqueline R. Rivas, Vivek M. Rangnekar, Natarajan Muthusamy, Subbarao Bondada
Summary: The study revealed that the spleen is the initial site of chronic lymphocytic leukemia (CLL) growth, with splenic stromal cells playing a crucial role in inducing CLL cell division. Splenectomy was found to delay CLL development, suggesting the importance of splenic stromal cells in CLL progression.
LEUKEMIA & LYMPHOMA
(2022)
Article
Multidisciplinary Sciences
Ben F. Brian, Monica L. Sauer, Joseph T. Greene, S. Erandika Senevirathne, Anders J. Lindstedt, Olivia L. Funk, Brian L. Ruis, Luis A. Ramirez, Jennifer L. Auger, Whitney L. Swanson, Myra G. Nunez, Branden S. Moriarity, Clifford A. Lowell, Bryce A. Binstadt, Tanya S. Freedman
Summary: This study reveals the distinct immunological functions of different splice variants of the Lyn kinase in vivo. LynB isoform exerts a dominant immunosuppressive function, while LynA isoform is uniquely required to restrain autoimmunity in female mice. Through gene editing, single-isoform LynA or LynB knockout mouse models were generated, showing isoform-specific and sexually dimorphic regulation of immune cell development and autoimmune diseases.
Article
Oncology
Mary K. McKenna, Ada Ozcan, Daniel Brenner, Norihiro Watanabe, Maureen Legendre, Dafydd G. Thomas, Christopher Ashwood, Richard D. Cummings, Challice Bonifant, David M. Markovitz, Malcolm K. Brenner
Summary: Researchers have developed a novel chimeric antigen receptor (CAR) based on plant lectins, which can recognize abnormal sugar residues on malignant cells and associated stromal cells. The CAR showed promising antitumor effects in models of pancreatic ductal adenocarcinoma (PDAC).
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Meeting Abstract
Immunology
Subbarao Bondada, James P. Collard, Mary Kathryn McKenna, Sunil K. Noothi, Sara S. Alhakeem, Jacqueline R. Rivas, Shelbi Broeking
JOURNAL OF IMMUNOLOGY
(2020)
Meeting Abstract
Ophthalmology
Ram Prasad, Jason L. Floyd, Dibyendu Chakraborty, Bright Asare-Bediako, Yvonne Adu-Agyeiwaah, Sergio Li Calzi, Robert F. Rosencrans, Chao Huang, Mariana DuPont, Sunil K. Noothi, Qiuhong Li, Maria B. Grant
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2020)
Article
Hematology
J. T. Greene, Rajeswaran Mani, Rahul Ramaswamy, Frank Frissora, Max Yano, Kevan Zapolnik, Bonnie Harrington, Ronni Wasmuth, Minh Tran, Xiaokui Mo, Mary McKenna, Vivek M. Rangnekar, John C. Byrd, Subbarao Bondada, Natarajan Muthusamy