title: A high rate of telomeric sister chromatid exchange occurs in chronic lymphocytic leukaemia B-cells.
abstract: 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.
authors.affiliation: Laboratory of Experimental Cancer Research, LIH, Luxembourg, Luxembourg.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Medves
authors.affiliation: Cancer Research Centre Marseille CRCM, U1068 Inserm, UMR7258 CNRS, Aix-Marseille University, Institut Paoli-Calmettes, Ligue Nationale contre le Cancer équipe labellisée, Marseille, France.
authors.forename: Morgan
authors.initials: M
authors.lastname: Auchter
authors.affiliation: Laboratory of Experimental Cancer Research, LIH, Luxembourg, Luxembourg.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Chambeau
authors.affiliation: Equipe Proliférations B Indolentes, Faculté de Médecine Lyon Sud, UMR CNRS 5239, Oullins Cedex, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gazzo
authors.affiliation: Biochemistry Department, Transfer and Molecular Oncology Unit, Lyon Sud Hospital, Hospices Civils de Lyon, Lyon, France.|Faculté de Médecine, UCBL Lyon 1, Oullins cedex 12, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Poncet
authors.affiliation: Biochemistry Department, Transfer and Molecular Oncology Unit, Lyon Sud Hospital, Hospices Civils de Lyon, Lyon, France.|Faculté de Médecine, UCBL Lyon 1, Oullins cedex 12, France.
authors.forename: Blandine
authors.initials: B
authors.lastname: Grangier
authors.affiliation: Equipe Proliférations B Indolentes, Faculté de Médecine Lyon Sud, UMR CNRS 5239, Oullins Cedex, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Verney
authors.affiliation: Laboratory of Experimental Cancer Research, LIH, Luxembourg, Luxembourg.
authors.forename: Etienne
authors.identifier: 0000-0002-0879-8067
authors.initials: E
authors.lastname: Moussay
authors.affiliation: Core Facility Flow Cytometry, Centre de Recherche Public de la Santé (CRP-Santé), Luxembourg, Luxembourg.
authors.forename: Wim
authors.initials: W
authors.lastname: Ammerlaan
authors.affiliation: Equipe Proliférations B Indolentes, Faculté de Médecine Lyon Sud, UMR CNRS 5239, Oullins Cedex, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Brisou
authors.affiliation: MEDyC, Unité CNRS UMR7369, UFR de Pharmacie, Reims, France.
authors.forename: Hamid
authors.initials: H
authors.lastname: Morjani
authors.affiliation: Cancer Research Centre Marseille CRCM, U1068 Inserm, UMR7258 CNRS, Aix-Marseille University, Institut Paoli-Calmettes, Ligue Nationale contre le Cancer équipe labellisée, Marseille, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Géli
authors.affiliation: Laboratory of Experimental Cancer Research, LIH, Luxembourg, Luxembourg.
authors.forename: Valérie
authors.initials: V
authors.lastname: Palissot
authors.affiliation: Laboratory of Experimental Cancer Research, LIH, Luxembourg, Luxembourg.
authors.forename: Guy
authors.initials: G
authors.lastname: Berchem
authors.affiliation: Equipe Proliférations B Indolentes, Faculté de Médecine Lyon Sud, UMR CNRS 5239, Oullins Cedex, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.affiliation: Laboratory of Experimental Cancer Research, LIH, Luxembourg, Luxembourg.|Equipe Proliférations B Indolentes, Faculté de Médecine Lyon Sud, UMR CNRS 5239, Oullins Cedex, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wenner
mesh_terms: D000328:Adult; D000368:Aged; D045566:DNA, Cruciform; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D012854:Sister Chromatid Exchange; D019098:Telomerase / Q000032:analysis; D016615:Telomere / Q000235:genetics*; D059505:Telomere Homeostasis
chemical_list: D045566:DNA, Cruciform; D019098:Telomerase
keywords: CLL; recombination; telomere; telomere maintenance mechanism; topoisomerase