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Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy.
Am J Hematol
January 2025
Department I of Internal Medicine and Medical Faculty, University of Cologne, Köln, Germany.
Disease Overview: Chronic lymphocytic leukemia (CLL) is the most frequent type of leukemia. It typically occurs in older patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and apoptosis in clonal B-cells.
View Article and Find Full Text PDFEffective eradication of acute myeloid leukemia stem cells with FLT3-directed antibody-drug conjugates.
Leukemia
January 2025
Department of Medicine III, LMU University Hospital, LMU Munich, Munich, Germany.
Refractory disease and relapse are major challenges in acute myeloid leukemia (AML) therapy attributed to survival of leukemic stem cells (LSC). To target LSCs, antibody-drug conjugates (ADCs) provide an elegant solution, combining the specificity of antibodies with highly potent payloads. We aimed to investigate if FLT3-20D9h3-ADCs delivering either the DNA-alkylator duocarmycin (DUBA) or the microtubule-toxin monomethyl auristatin F (MMAF) can eradicate quiescent LSCs.
View Article and Find Full Text PDFIdentification of a novel TOP2B::AFF2 fusion gene in B-cell acute lymphoblastic leukemia.
Sci Rep
January 2025
Department of Hematology and Oncology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Children's Hospital of Chongqing Medical University, No 136 Zhongshan 2 road, YuZhong district, Chongqing, 400014, China.
Genetic alterations play a pivotal role in leukemic clonal transformation, significantly influencing disease pathogenesis and clinical outcomes. Here, we report a novel fusion gene and investigate its pathogenic role in acute lymphoblastic leukemia (ALL). We engineer a transposon transfection system expressing the TOP2B::AFF2 transcript and introduce it into Ba/F3 cells.
View Article and Find Full Text PDFPROTAC-Mediated GSPT1 Degradation Impairs the Expression of Fusion Genes in Acute Myeloid Leukemia.
Cancers (Basel)
January 2025
Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.
Background: Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that utilize the ubiquitin-proteasome system to selectively degrade target proteins. This innovative technology has shown remarkable efficacy and specificity in degrading oncogenic proteins and has progressed through various stages of preclinical and clinical development for hematologic malignancies, including adult acute myeloid leukemia (AML). However, the application of PROTACs in pediatric AML remains largely unexplored.
View Article and Find Full Text PDFExtracellular vesicles from chronic lymphocytic leukemia cells promote leukemia aggressiveness by inducing the differentiation of monocytes into nurse-like cells via an RNA-dependent mechanism.
Hemasphere
January 2025
Laboratory of Clinical Cell Therapy Université Libre de Bruxelles (ULB), Jules Bordet Institute Brussels Belgium.
Chronic lymphocytic leukemia (CLL) cells receive several stimuli from surrounding cells, such as B-cell receptor (BCR) stimulation, and can manipulate their microenvironment via extracellular vesicle (EV) release. Here, we investigated the small RNA content (microRNA and YRNA) of CLL-EVs from leukemic cells cultured with/without BCR stimulation. We highlight an increase of miR-155-5p, miR-146a-5p, and miR-132-3p in EVs and in cells after BCR stimulation ( < 0.
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