keyword
https://read.qxmd.com/read/37930156/first-in-human-study-of-the-reversible-btk-inhibitor-nemtabrutinib-in-patients-with-relapsed-refractory-chronic-lymphocytic-leukemia-and-b-cell-non-hodgkin-lymphoma
#21
JOURNAL ARTICLE
Jennifer A Woyach, Deborah M Stephens, Ian W Flinn, Seema A Bhat, Ronald E Savage, Feng Chai, Sudharshan Eathiraj, Sean D Reiff, Elizabeth M Muhowski, Lindsey Granlund, Lyndsey Szuszkiewicz, Wayne Wang, Brian Schwartz, Razi Ghori, Mohammed Z H Farooqui, John C Byrd
UNLABELLED: Nemtabrutinib is an orally bioavailable, reversible inhibitor of Bruton tyrosine kinase (BTK) and C481S mutant BTK. We evaluated the safety, pharmacology, and antitumor activity of nemtabrutinib in relapsed/refractory hematologic malignancies. Forty-eight patients with chronic lymphocytic leukemia (CLL), B-cell non-Hodgkin lymphoma (NHL), or Waldenström macroglobulinemia (WM), relapsed/refractory after ≥2 prior therapies were enrolled in the open-label, single-arm, phase I MK-1026-001 study (NCT03162536) to receive nemtabrutinib 5 to 75 mg once daily in 28-day cycles...
January 12, 2024: Cancer Discovery
https://read.qxmd.com/read/37899943/intravenous-immunoglobulin-therapy-induced-erythema-multiforme-in-a-patient-with-chronic-lymphocytic-leukemia
#22
Angelina Konovalova, Natālija Gerula, Ilona Hartmane, Ilze Upeniece, Mihails Ščerbuks, Kristīne Bernāte, Lelde Reinberga, Ingmārs Mikažāns
This case report discusses immunoglobulin-induced erythema multiforme (EM), a rare and understudied condition that requires further investigation. The report presents the case of a 69-year-old woman with a history of chronic lymphocytic leukemia who developed an acute hypersensitivity reaction to intravenous gamma globulin medication. The patient received intravenous immunoglobulin (IVIG) to normalize and stabilize her immunoglobulin levels and reduce the risk of recurrent infections due to her immunodeficiency with predominantly antibody defects...
2023: Case Reports in Dermatology
https://read.qxmd.com/read/37894699/an-ultrafast-uplc-ms-ms-method-for-characterizing-the-in-vitro-metabolic-stability-of-acalabrutinib
#23
JOURNAL ARTICLE
Mohamed W Attwa, Ahmed H Bakheit, Ali S Abdelhameed, Adnan A Kadi
Acalabrutinib, commercially known as Calquence® , is a pharmacological molecule that has robust inhibitory activity against Bruton tyrosine kinase. The medicine in question was carefully developed by the esteemed pharmaceutical company AstraZeneca. The FDA granted authorization on 21 November 2019 for the utilization of acalabrutinib (ACB) in the treatment of small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) in adult patients. The aim of this study was to develop a UPLC-MS/MS method that is effective, accurate, environmentally sustainable, and has a high degree of sensitivity...
October 23, 2023: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/37871223/expression-signature-of-human-endogenous-retroviruses-in-chronic-lymphocytic-leukemia
#24
JOURNAL ARTICLE
Alessandro La Ferlita, Giovanni Nigita, Liudmyla Tsyba, Alexey Palamarchuk, Salvatore Alaimo, Alfredo Pulvirenti, Veronica Balatti, Laura Rassenti, Philip N Tsichlis, Thomas Kipps, Yuri Pekarsky, Carlo M Croce
Chronic lymphocytic leukemia (CLL) is one of the most diagnosed forms of leukemia worldwide and it is usually classified into two forms: indolent and aggressive. These two forms are characterized by distinct molecular features that drive different responses to treatment and clinical outcomes. In this context, a better understanding of the molecular landscape of the CLL forms may potentially lead to the development of new drugs or the identification of novel biomarkers. Human endogenous retroviruses (HERVs) are a class of transposable elements that have been associated with the development of different human cancers, including different forms of leukemias...
October 31, 2023: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/37848261/asymmetric-anti-cll-1%C3%A3-cd3-bispecific-antibody-abl602-2-1-with-attenuated-cd3-affinity-endows-potent-antitumor-activity-but-limited-cytokine-release
#25
JOURNAL ARTICLE
Eunhee Lee, Shinai Lee, Sumyeong Park, Yong-Gyu Son, Jiseon Yoo, Youngil Koh, Dong-Yeop Shin, Yangmi Lim, Jonghwa Won
BACKGROUND: Acute myeloid leukemia (AML) is a type of leukemia in adults with a high mortality rate and poor prognosis. Although targeted therapeutics, chemotherapy, and hematopoietic stem cell transplantation can improve the prognosis, the recurrence rate is still high, with a 5-year survival rate of approximately 40%. This study aimed to develop an IgG-based asymmetric bispecific antibody that targets CLL-1 and CD3 for treating AML. METHODS: ABL602 candidates were compared in terms of binding activity, T-cell activation, and tumor-killing activities...
October 2023: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/37830752/measurement-of-trogocytosis-quantitative-analyses-validated-with-rigorous-controls
#26
JOURNAL ARTICLE
Ronald P Taylor, Margaret A Lindorfer
Trogocytosis is a process in which receptors on acceptor cells remove and internalize cognate ligands from donor cells. Trogocytosis has a profound and negative impact on mAb-based cancer immunotherapy, as seen in the treatment of chronic lymphocytic leukemia (CLL) with CD20 mAbs, such as rituximab (RTX) and ofatumumab (OFA). Our clinical observations of RTX/OFA-mediated loss of the CD20 target from circulating CLL cells have been replicated in our in vitro studies. Here we describe flow cytometry and fluorescence microscopy experiments, which demonstrate that acceptor cells, such as monocytes/macrophages that express FcγR, remove and internalize both antigen and donor cell-bound cognate IgG mAbs for several different mAb-donor cell pairs...
October 2023: Current protocols
https://read.qxmd.com/read/37817276/regulatory-t-cells-contribute-to-the-immunosuppressive-phenotype-of-neutrophils-in-a-mouse-model-of-chronic-lymphocytic-leukemia
#27
JOURNAL ARTICLE
Agnieszka Goral, Marta Sledz, Aneta Manda-Handzlik, Adrianna Cieloch, Alicja Wojciechowska, Mieszko Lachota, Agnieszka Mroczek, Urszula Demkow, Radoslaw Zagozdzon, Katarzyna Matusik, Malgorzata Wachowska, Angelika Muchowicz
BACKGROUND: Impaired neutrophil activity is an important issue in chronic lymphocytic leukemia (CLL), as it contributes to a dysfunctional immune response leading to life-threatening infections in patients. Some features typical of CLL neutrophils, e.g., the B-cell-supportive secretion profile, have already been described. However, most of these studies were performed on cells isolated from peripheral blood. It is still unclear which molecular factors and cell types are involved in shaping neutrophil function and phenotype in the CLL microenvironment...
October 10, 2023: Experimental Hematology & Oncology
https://read.qxmd.com/read/37786827/-in-vitro-modulation-of-mtor-hif-1%C3%AE-axis-by-tlr7-8-agonist-resiquimod-in-b-chronic-lymphocytic-leukemia
#28
JOURNAL ARTICLE
Rana M Hanafy, Soheir R Demian, Lobna A Abou-Shamaa, O Ghallab, Eman M Osman
UNLABELLED: Targeting toll-like receptors (TLRs), via TLR agonists, has been implicated in the regulation of immunometabolism. B-chronic lymphocytic leukemia (B-CLL) represents a suitable model for B-cell derived malignancies with shifted metabolic adaptations. Several signaling pathways have been found to be critical in metabolic reprogramming of CLL, including mechanistic target of rapamycin- hypoxia inducible factor-1α (mTOR- HIF-1α) pathway, the main metabolic regulator of glycolysis...
October 2023: Indian Journal of Hematology & Blood Transfusion
https://read.qxmd.com/read/37749039/-efficacy-and-safety-of-tbi-ratg-based-conditioning-regimen-for-haploidentical-allogeneic-hematopoietic-stem-cell-transplantation-in-11-cases-of-chemotherapy-resistant-advanced-peripheral-t-cell-lymphoma
#29
JOURNAL ARTICLE
R Xu, S Li, H X Liu, D L Wei, Y Jiang, J J Wang, S S Liu, C Wang, J Zhu
Objective: To evaluate the clinical outcomes and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using a conditioning regimen based on total body irradiation (TBI) and rabbit anti-human thymocyte globulin (rATG) in the management of chemotherapy-resistant advanced peripheral T-cell lymphoma (PTCL) . Methods: Clinical data of 11 patients with chemotherapy-resistant advanced PTCL who underwent haplo-HSCT with a TBI+rATG-based conditioning regimen at the Department of Hematology, Shanghai Liquan Hospital and Shanghai Zhaxin Integrated Traditional Chinese and Western Medicine Hospital, from September 2019 to December 2022 were retrospectively analyzed...
July 14, 2023: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://read.qxmd.com/read/37745292/a-comparative-analysis-of-gene-and-protein-expression-in-chronic-and-acute-models-of-photoreceptor-degeneration-in-adult-zebrafish
#30
JOURNAL ARTICLE
Ashley C Kramer, Justin Carthage, Yasmeen Berry, Katherine Gurdziel, Tiffany A Cook, Ryan Thummel
Background: Adult zebrafish are capable of photoreceptor (PR) regeneration following acute phototoxic lesion (AL). We developed a chronic low light (CLL) exposure model that more accurately reflects chronic PR degeneration observed in many human retinal diseases. Methods: Here, we characterize the morphological and transcriptomic changes associated with acute and chronic models of PR degeneration at 8 time-points over a 28-day window using immunohistochemistry and 3'mRNA-seq. Results: We first observed a differential sensitivity of rod and cone PRs to CLL...
2023: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/37726507/lifetime-exposure-to-brominated-trihalomethanes-in-drinking-water-and-swimming-pool-attendance-are-associated-with-chronic-lymphocytic-leukemia-a-multicase-control-study-in-spain-mcc-spain
#31
JOURNAL ARTICLE
Carolina Donat-Vargas, Manolis Kogevinas, Yolanda Benavente, Laura Costas, Elias Campo, Gemma Castaño-Vinyals, Guillermo Fernandez-Tardon, Javier Llorca, Inés Gómez-Acebo, Nuria Aragonés, Marina Pollan, Delphine Casabonne, Cristina M Villanueva
BACKGROUND: Chronic lymphocytic leukemia (CLL) etiology is poorly understood, and carcinogenic chemicals in drinking and recreational water are candidates. OBJECTIVE: To evaluate the association between drinking-water exposure to trihalomethanes (THMs) and nitrate as well as lifetime swimming pool attendance and CLL. METHODS: During 2010-2013, hospital-based CLL cases and population-based controls were recruited in Spain, providing information on residential histories, type of water consumed and swimming pool attendance...
September 19, 2023: Journal of Exposure Science & Environmental Epidemiology
https://read.qxmd.com/read/37724003/lc-ms-ms-methods-for-determination-of-venetoclax-in-human-plasma-and-cerebrospinal-fluid
#32
JOURNAL ARTICLE
Yan-Ling Yang, Zhou-Yi Qian, Yang Zhao, Xiang-Long Chen, Qiong-Ye Huang, Yu-Jiao Guo, Lu-Ning Sun, Yong-Qing Wang
We developed and validated sensitive MS/MS methods for the determination of venetoclax, an oral selective B-cell lymphoma-2 inhibitor, in human plasma and cerebrospinal fluid (CSF). Acetonitrile was used as protein precipitant. The mobile phase was 10 mM ammonium formate consisting of 0.1% formic acid and acetonitrile (40:60, v/v). The analytes were separated on an ACQUITY UPLC HSS T3 column (2.1 × 50 mm, 1.8 μm) in 5 min. An API 4000 mass spectrometer was selected to quantify venetoclax and internal standard using m/z 868...
September 18, 2023: Biomedical Chromatography: BMC
https://read.qxmd.com/read/37712633/tandem-bispecific-cd123-cll-1-car-t-cells-exhibit-specific-cytolytic-effector-functions-against-human-acute-myeloid-leukaemia
#33
JOURNAL ARTICLE
Xiang-Yu Wang, Mei-Ru Bian, Guo-Qiang Lin, Lei Yu, Yan-Ming Zhang, De-Pei Wu
OBJECTIVES: The treatment of refractory and recurrent acute myeloid leukaemia (AML) is still a challenge with poor response rates and short survival times. In an attempt to solve this problem, we constructed a tandem bispecific chimeric antigen receptor (CAR) targeting CD123 and C-type lectin-like molecule 1 (CLL-1), two different AML antigens, and verified its cytotoxic effects in vitro. METHODS: We established and cultured K562 cell lines expressing both CD123 and CLL1 antigens...
January 2024: European Journal of Haematology
https://read.qxmd.com/read/37699659/nucleosome-repositioning-in-chronic-lymphocytic-leukaemia
#34
JOURNAL ARTICLE
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
The location of nucleosomes in the human genome determines the primary chromatin structure and regulates access to regulatory regions. However, genome-wide information on deregulated nucleosome occupancy and its implications in primary cancer cells is scarce. Here, we conducted a genome-wide comparison of high-resolution nucleosome maps in peripheral-blood B cells from patients with chronic lymphocytic leukaemia (CLL) and healthy individuals at single base pair resolution. Our investigation uncovered significant changes of nucleosome positioning in CLL...
September 12, 2023: Genome Research
https://read.qxmd.com/read/37696810/zanubrutinib-past-present-and-future
#35
REVIEW
Constantine S Tam, Javier L Muñoz, John F Seymour, Stephen Opat
In recent years, Bruton tyrosine kinase (BTK) inhibitors have provided significant advances in the treatment of patients with B-cell malignancies. Ibrutinib was the first BTK inhibitor to be approved, and it changed the standard-of-care treatment for diseases such as chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and Waldenström macroglobulinemia, improving efficacy outcomes and safety compared to chemotherapy. In this article, we review the development of zanubrutinib, a next-generation BTK inhibitor, from molecular design to patient-related outcomes...
September 11, 2023: Blood Cancer Journal
https://read.qxmd.com/read/37676018/the-hpv8-e6-protein-targets-the-hippo-and-wnt-signaling-pathways-as-part-of-its-arsenal-to-restrain-keratinocyte-differentiation
#36
JOURNAL ARTICLE
Sharon C Wu, Miranda Grace, Karl Munger
Infections with β-genus human papillomaviruses (HPVs) cause hyperplastic cutaneous lesions. In individuals with the rare hereditary skin disease, epidermodysplasia verruciformis, such lesions can progress to cutaneous squamous cell carcinomas (cSCCs). β-HPV infections may also underlie cSCC development in chronically immunosuppressed individuals. Despite their prevalence and disease association, these viruses are not as well studied as the cancer-associated high-risk α-genus HPVs. HPV-associated lesions are characterized by a marked expansion of dividing, basal-like, poorly differentiated viral cells that contain viral genomes...
September 7, 2023: MBio
https://read.qxmd.com/read/37661406/cdk9-inhibitor-induces-apoptosis-autophagy-and-suppression-of-tumor-growth-in-adult-t-cell-leukemia-lymphoma
#37
JOURNAL ARTICLE
Naho Kato, Tomohiro Kozako, Takeo Ohsugi, Yuichiro Uchida, Makoto Yoshimitsu, Kenji Ishitsuka, Akiyoshi Aikawa, Shin-Ichiro Honda
Adult T-cell leukemia/lymphoma (ATL) is a hematopoietic malignancy with a poor prognosis that develops in approximately 5% of human T-cell leukemia virus type 1 (HTLV-1) carriers. Cyclin-dependent kinase 9 (CDK9), together with Cyclin T, forms a transcription elongation factor, positive transcription elongation factor b (P-TEFb). P-TEFb promotes transcriptional elongation by phosphorylating the second serine (Ser2) of the seven amino acid repeat sequence in the C-terminal domain of RNA polymerase II (RNAP II)...
2023: Biological & Pharmaceutical Bulletin
https://read.qxmd.com/read/37655260/studying-the-dna-damage-response-pathway-in-hematopoietic-canine-cancer-cell-lines-a-necessary-step-for-finding-targets-to-generate-new-therapies-to-treat-cancer-in-dogs
#38
JOURNAL ARTICLE
Beatriz Hernández-Suárez, David A Gillespie, Ewa Dejnaka, Piotr Kupczyk, Bożena Obmińska-Mrukowicz, Aleksandra Pawlak
BACKGROUND: Dogs present a significant opportunity for studies in comparative oncology. However, the study of cancer biology phenomena in canine cells is currently limited by restricted availability of validated antibody reagents and techniques. Here, we provide an initial characterization of the expression and activity of key components of the DNA Damage Response (DDR) in a panel of hematopoietic canine cancer cell lines, with the use of commercially available antibody reagents. MATERIALS AND METHODS: The techniques used for this validation analysis were western blot, qPCR, and DNA combing assay...
2023: Frontiers in Veterinary Science
https://read.qxmd.com/read/37654003/effects-of-blocking-cd24-and-cd47-don-t-eat-me-signals-in-combination-with-rituximab-in-mantle-cell-lymphoma-and-chronic-lymphocytic-leukaemia
#39
JOURNAL ARTICLE
Andrea Aroldi, Mario Mauri, Daniele Ramazzotti, Matteo Villa, Federica Malighetti, Valentina Crippa, Federica Cocito, Chiara Borella, Elisa Bossi, Carolina Steidl, Chiara Scollo, Claudia Voena, Roberto Chiarle, Luca Mologni, Rocco Piazza, Carlo Gambacorti-Passerini
Mantle-cell lymphoma (MCL) is a B-cell non-Hodgkin Lymphoma (NHL) with a poor prognosis, at high risk of relapse after conventional treatment. MCL-associated tumour microenvironment (TME) is characterized by M2-like tumour-associated macrophages (TAMs), able to interact with cancer cells, providing tumour survival and resistance to immuno-chemotherapy. Likewise, monocyte-derived nurse-like cells (NLCs) present M2-like profile and provide proliferation signals to chronic lymphocytic leukaemia (CLL), a B-cell malignancy sharing with MCL some biological and phenotypic features...
August 31, 2023: Journal of Cellular and Molecular Medicine
https://read.qxmd.com/read/37629695/a-nine-gene-expression-signature-distinguished-a-patient-with-chronic-lymphocytic-leukemia-who-underwent-prolonged-periodic-fasting
#40
JOURNAL ARTICLE
Luca Emanuele Bossi, Cassandra Palumbo, Alessandra Trojani, Agostina Melluso, Barbara Di Camillo, Alessandro Beghini, Luca Maria Sarnataro, Roberto Cairoli
Background and Objectives : This study aimed to investigate the causes of continuous deep fluctuations in the absolute lymphocyte count (ALC) in an untreated patient with Chronic Lymphocytic Leukemia (CLL), who has had a favorable prognosis since the time of diagnosis. Up until now, the patient has voluntarily chosen to adopt a predominantly vegetarian and fruitarian diet, along with prolonged periods of total fasting (ranging from 4 to 39 days) each year. Materials and Methods : For this purpose, we decided to analyze the whole transcriptome profiling of peripheral blood (PB) CD19+ cells from the patient (#1) at different time-points vs...
July 31, 2023: Medicina
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