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A high rate of telomeric sister chromatid exchange occurs in chronic lymphocytic leukaemia B‐cells
Author(s) -
Medves Sandrine,
Auchter Morgan,
Chambeau Laetitia,
Gazzo Sophie,
Poncet Delphine,
Grangier Blandine,
Verney Aurélie,
Moussay Etienne,
Ammerlaan Wim,
Brisou Gabriel,
Morjani Hamid,
Géli Vincent,
Palissot Valérie,
Berchem Guy,
Salles Gilles,
Wenner Thomas
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13995
Subject(s) - telomere , telomerase , microbiology and biotechnology , sister chromatids , biology , chronic lymphocytic leukemia , sister chromatid exchange , chromosome instability , shelterin , cancer research , genetics , dna , chromosome , leukemia , gene , dna binding protein , transcription factor
Summary 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 ( TOP 3A ) expression, involved in the dissolution of Holliday Junctions ( HJ ), together with an increased expression of SLX 1A , SLX 4 , MUS 81 and GEN 1 , 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.