Dynamic changes in clonal cytogenetic architecture during progression of chronic lymphocytic leukemia in patients and patient-derived murine xenografts

Nicholas Davies, Marwan Kwok, Clive Gould, Ceri Oldreive, Jingwen Mao, Helen Parry, Edward Smith, Angelo Agathanggelou, Guy Pratt, Malcolm Taylor, Paul Moss, Mike Griffiths, Tatjana Stankovic

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7 Citations (Scopus)
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Abstract

Cytogenetic aberrations shape the clinical course and often treatment response in chronic lymphocytic leukemia (CLL). Therefore, the evaluation of cytogenetic abnormalities by FISH remains an important part of patients’ diagnostic evaluation. We demonstrate that application of patient-specific combination of FISH probes against clinically relevant genomic regions can enhance recognition of the subclonal repertoire and enable determination of the evolutionary dynamics of CLL cytogenetic aberrations during disease progression at the single-cell level. The significance of this study lies in the demonstration that treatment-induced clonal dynamics can be modelled in vivo, where it can be readily distinguished from spontaneous clonal progression. This strategy can be applied to evaluate novel CLL therapies in the pre-clinical setting, and to inform treatment choice for patients with differing cytogenetic composition, including those with adverse features or complex karyotype.
Original languageEnglish
Pages (from-to)44749-44760
JournalOncoTarget
Volume8
Issue number27
DOIs
Publication statusPublished - 26 Apr 2017

Keywords

  • chronic lymphocytic leukaemia
  • xenograft
  • clonal evolution
  • multiplexed-FISH
  • cytogenetics

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