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Association of Genetic Variants at the and Loci Encoding p27 and Cyclin D2 Cell Cycle Regulators with Susceptibility and Clinical Course of Chronic Lymphocytic Leukemia.
Int J Mol Sci
October 2024
Clinical Department of Hematology, Cell Therapies and Internal Diseases, Wroclaw Medical University, 50-367 Wroclaw, Poland.
Beyond the essential role of p27 and cyclin D2 in cell cycle progression, they are also shown to confer an anti-apoptotic function in peripheral blood (PB) lymphocytes. Although the aberrant longevity and expression of p27 and cyclin D2 in leukemic cells is well documented, the exact mechanisms responsible for this phenomenon have yet to be elucidated. This study was undertaken to determine the associations between polymorphisms in the and genes (encoding p27 and cyclin D2, respectively) and susceptibility to chronic lymphocytic leukemia (CLL), as well as their influence on the expression of both cell cycle regulators in PB leukemic B cells and non-malignant T cells from untreated CLL patients divided according to the genetic determinants studied.
View Article and Find Full Text PDFGenome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy.
Nat Commun
September 2024
Division of Endocrinology, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Article Synopsis
- - The study investigates the link between insulin resistance and various metabolic diseases, emphasizing the need to consider insulin resistance in epidemiological studies.
- - By analyzing genetic data from over 382,000 individuals, researchers identified 251 genetic loci related to insulin resistance and prioritized key genes through further analysis.
- - Notable findings include genes like PLA2G12A and PLA2G6, which enhance insulin sensitivity, and TNFAIP8, which affects insulin resistance differently in females by increasing fat accumulation; these could be potential biomarkers or drug targets.
CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity.
Cells
June 2024
Department of Dermatology, University Hospital Zurich, CH-8952 Schlieren, Switzerland.
Inflammasomes comprise a group of protein complexes with fundamental roles in the induction of inflammation. Upon sensing stress factors, their assembly induces the activation and release of the pro-inflammatory cytokines interleukin (IL)-1β and -18 and a lytic type of cell death, termed pyroptosis. Recently, CARD8 has joined the group of inflammasome sensors.
View Article and Find Full Text PDFPreclinical Characterization of the Anti-Leukemia Activity of the CD33/CD16a/NKG2D Immune-Modulating TriNKET CC-96191.
Cancers (Basel)
February 2024
Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Increasing efforts are focusing on natural killer (NK) cell immunotherapies for AML. Here, we characterized CC-96191, a novel CD33/CD16a/NKG2D immune-modulating TriNKET. CC-96191 simultaneously binds CD33, NKG2D, and CD16a, with NKG2D and CD16a co-engagement increasing the avidity for, and activation of, NK cells.
View Article and Find Full Text PDFPerturbational phenotyping of human blood cells reveals genetically determined latent traits associated with subsets of common diseases.
Nat Genet
January 2024
One Brave Idea and Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Article Synopsis
- GWAS have linked genetic risk to diseases, but understanding the cellular mechanisms is tough due to disease complexity.
- We created a framework using human blood cells and various methods to uncover these cellular processes, conducting GWAS with data from 2,600 individuals and identifying 119 genomic loci related to immune responses.
- We found a specific type of neutrophil linked to cardiometabolic diseases and developed a model predicting chronic kidney disease risk in type 2 diabetes patients, which helps advance patient stratification and biological understanding in genetic studies.
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