The nuclear arrangement of promyelocytic leukaemia nuclear bodies (PML NBs) was studied in vitro after the cell treatment by clinically used agents such as all-trans retinoic acid (RA) in human leukaemia and cytostatics or gamma radiation in multiple myeloma cells. In addition, the influence of phorbol ester (PMA) on PML NBs formation was analyzed. A reduced number of PML bodies, which led to relocation of PML NBs closer to the nuclear interior, mostly accompanied RA- and PMA-induced differentiation. Centrally located PML NBs were associated with transcriptional protein RNAP II and SC35 regions, which support importance of PML NBs in RNA processing that mostly proceeds within the nuclear interior. Conversely, the quantity of PML NBs was increased after cytostatic treatment, which caused re-distribution of PML NBs closer to the nuclear envelope. Here we showed correlations between the number of PML NBs and average Centre-to-PML distances. Moreover, a number of cells in S phase, especially during differentiation, influenced number of PML NBs. Studying the proteins involved in PML compartment, such as c-MYC, cell-type specific association of c-MYC and the PML NBs was observed in selected leukaemic cells undergoing differentiation, which was accompanied by c-MYC down-regulation.
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http://dx.doi.org/10.1016/j.leukres.2008.04.021 | DOI Listing |
J Mol Biol
January 2025
Department of Biology, Carnegie Mellon University, Pittsburgh, PA 15213, USA. Electronic address:
Alternative Lengthening of Telomeres (ALT) pathway is a telomerase-independent mechanism that utilizes homology-directed repair (HDR) to sustain telomere length in specific cancers. Biomolecular condensates, such as ALT-associated promyelocytic leukemia nuclear bodies (APBs), have emerged as critical players in the ALT pathway, supporting telomere maintenance in ALT-positive cells. These condensates bring together DNA repair proteins, telomeric repeats, and other regulatory elements.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
IKKε is a traditional antiviral kinase known for positively regulating the production of type I interferon (IFN) and the expression of IFN-stimulated genes (ISGs) during various virus infections. However, through an inhibitor screen targeting cellular kinases, we found that IKKε plays a crucial role in the lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV). Mechanistically, during KSHV lytic replication, IKKε undergoes significant SUMOylation at both Lys321 and Lys549 by the viral SUMO E3 ligase ORF45.
View Article and Find Full Text PDFMedicine (Baltimore)
November 2024
Clinical laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.
This study analyzes the laboratory characteristics and prognosis of patients between PML-RARα negative APL and PML-RARα positive APL and compares the differences in order to improve the understanding of this rare APL and guide clinical diagnosis and treatment. A total of 81 patients with newly diagnosed APL based on bone marrow cell morphology were included, with 14 in the PML-RARα gene negative group and 67 in the PML-RARα gene positive group. The sex, age, peripheral blood routine test, coagulation related indicators, bone marrow cell morphology, flow cytometric immunophenotype, abnormal chromosome expression and prognosis of the 2 groups were analyzed and compared.
View Article and Find Full Text PDFCytopathology
January 2025
Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
This is the first case report describing the diagnostic value of dot-shaped inclusions associated with promyelocytic leukaemia nuclear bodies (PML-NBs) to define JC virus-infected glial cells in an intraoperative cytopathological diagnosis for progressive multifocal leukoencephalopathy (PML).
View Article and Find Full Text PDFCells
December 2024
Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky av.4, 194064 St. Petersburg, Russia.
Natural aging and age-related diseases involve the acceleration of replicative aging, or senescence. Multiple proteins are known to participate in these processes, including the promyelocytic leukemia (PML) protein, which serves as a core component of nuclear-membrane-less organelles known as PML nuclear bodies (PML-NBs). In this work, morphological changes in PML-NBs and alterations in PML protein localization at the transition of primary fibroblasts to a replicative senescent state were studied by immunofluorescence.
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