1. A high rate of telomeric sister chromatid exchange occurs in chronic lymphocytic leukaemia B-cells
- Author
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Guy Berchem, Hamid Morjani, Sophie Gazzo, Gabriel Brisou, Laetitia Chambeau, Morgan Auchter, Wim Ammerlaan, Aurélie Verney, Valérie Palissot, Etienne Moussay, Vincent Géli, Gilles Salles, Blandine Grangier, Sandrine Medves, Delphine Poncet, Thomas Wenner, Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Ciblage thérapeutique en Oncologie ( EA3738 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Adult ,0301 basic medicine ,Telomerase ,Patients ,Cells ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Sister chromatid exchange ,Biology ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,Telomere Homeostasis ,Humans ,Aged ,DNA, Cruciform ,Hematology ,Middle Aged ,Telomere ,Shelterin ,Flow Cytometry ,Leukemia, Lymphocytic, Chronic, B-Cell ,MUS81 ,Molecular biology ,030104 developmental biology ,Cancer cell ,France ,Homologous recombination ,Laboratories ,Sister Chromatid Exchange - Abstract
International audience; Cancer cells protect their telomere ends from erosion through reactivation of telomerase or by using the Alternative Lengthening of Telomere (ALT) mechanism that depends on homologous recombination. Chronic lymphocytic leukaemia (CLL) B cells are characterized by almost no telomerase activity, shelterin deregulation and telomere fusions. To characterize telomeric maintenance mechanisms in B-CLL patients, we measured their telomere length, telomerase expression and the main hallmarks of the ALT activity i.e. C-circle concentration, an extra-chromosomal telomere repeat (ECTR), and the level of telomeric sister chromatid exchange (T-SCE) rate. Patients showed relative homogenous telomere length although almost no TERT transcript and nearly no C-circle were evidenced. Nevertheless, compared with normal B cells, B-CLL cells showed an increase in T-SCE rate that was correlated with a strong down-regulation of the topoisomerase III alpha (TOP3A) expression, involved in the dissolution of Holliday Junctions (HJ), together with an increased expression of SLX1A, SLX4, MUS81 and GEN1, involved in the resolution of HJ. Altogether, our results suggest that the telomere maintenance mechanism of B-CLL cells do not preferentially use telomerase or ALT. Rather, the rupture of the dissolvasome/resolvasome balance may increase telomere shuffling that could homogenize telomere length, slowing telomere erosion in this disease
- Published
- 2016
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