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Molecular Composition and Kinetics of B Cells During Ibrutinib Treatment in Patients with Chronic Lymphocytic Leukemia.
Int J Mol Sci
November 2024
Haematology-Pathology Research Laboratory, Research Unit for Haematology and Research Unit for Pathology, University of Southern Denmark and Odense University Hospital, 5000 Odense, Denmark.
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B cells due to constitutive B-cell receptor (BCR) signaling, leading to apoptosis resistance and increased proliferation. This study evaluates the effects of the Bruton Tyrosine Kinase (BTK) inhibitor ibrutinib on the molecular composition, clonality, and kinetics of B cells during treatment in CLL patients. Employing a multi-omics approach of up to 3.
View Article and Find Full Text PDFReal-World Evidence on Adverse Events and Healthcare Resource Utilization in Patients with Chronic Lymphocytic Leukaemia in Spain Using Natural Language Processing: The SRealCLL Study.
Cancers (Basel)
November 2024
Haematology Department, Hospital Universitario de la Princesa, 28004 Madrid, Spain.
The SRealCLL study described the occurrence of adverse events (AEs) and healthcare resource utilization in patients with chronic lymphocytic leukaemia (CLL) using artificial intelligence in a real-world scenario in Spain. We collected real-world data on patients with CLL from seven Spanish hospitals between January 2016 and December 2018, focusing on their AE and healthcare service utilization. Data extraction from electronic health records of 385,904 patients was performed using the EHRead technology, which is based on natural language processing and machine learning.
View Article and Find Full Text PDFThe evolving frontline management of CLL: are triplets better than doublets? How will we find out?
Hematology Am Soc Hematol Educ Program
December 2024
Division of Hematology, The Ohio State University, Columbus, OH.
Frontline therapy for chronic lymphocytic leukemia (CLL) has substantially advanced in the previous decade. While monotherapy with a Bruton's tyrosine kinase (BTK) inhibitor is an excellent option for many patients, combination therapies are of high clinical interest as they can induce deep responses and durable remissions, and in many cases allow discontinuation of therapy. There are several doublet therapies that are currently in clinical use.
View Article and Find Full Text PDFAberrantly Expressed Mitochondrial Lipid Kinase, AGK Activates JAK2-Histone H3 Axis and BCR Signal: A Mechanistic Study with Implication in CLL Therapy.
Clin Cancer Res
December 2024
University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
Purpose: Although the B-cell receptor (BCR) signal plays a critical role in CLL cell survival and a target of current therapies (ibrutinib targets Bruton's tyrosine kinase; idelalisib targets PI3Kδ), contribution of the cytokine-driven JAK2 pathway to the "CLL cell-survival signaling network" is largely undefined.
Experimental Design: CLL patients were enrolled to investigate expression/activation of JAK2 and acylglycerol kinase (AGK), and their functional implication in primary CLL cell survival. A series of biochemical and molecular biology assays were employed to uncover the underlying mechanism.
Multi-Component, Time-Course screening to develop combination cancer therapies based on synergistic toxicity.
Proc Natl Acad Sci U S A
December 2024
Division of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, MD 20850.
Article Synopsis
- Clinical trials for cancer treatments should be based on strong scientific understanding and proven drug effectiveness in relevant disease models.
- This study examines the effects of four small-molecule drugs on lymphoma cell lines, revealing that synergistic combinations effectively induce cell death (apoptosis) in a way that mimics actual drug exposure in patients.
- The findings suggest that in vitro drug screening can help identify effective drug combinations that leverage their synergistic effects to tackle the complexity of human cancers, especially in diverse genetic lymphoma models.
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