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

doi:10.18632/oncotarget.17432

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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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 language	English
Pages (from-to)	44749-44760
Journal	OncoTarget
Volume	8
Issue number	27
DOIs	https://doi.org/10.18632/oncotarget.17432
Publication status	Published - 26 Apr 2017

Keywords

chronic lymphocytic leukaemia
xenograft
clonal evolution
multiplexed-FISH
cytogenetics

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10.18632/oncotarget.17432Licence: Creative Commons: Attribution (CC BY)

Davies et al 2017Final published version, 3.01 MBLicence: Creative Commons: Attribution (CC BY)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546515/Licence: Creative Commons: Attribution (CC BY)

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Davies, N., Kwok, M., Gould, C., Oldreive, C., Mao, J., Parry, H., Smith, E., Agathanggelou, A., Pratt, G., Taylor, M., Moss, P., Griffiths, M., & Stankovic, T. (2017). Dynamic changes in clonal cytogenetic architecture during progression of chronic lymphocytic leukemia in patients and patient-derived murine xenografts. OncoTarget, 8(27), 44749-44760. https://doi.org/10.18632/oncotarget.17432

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

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{\textquoteright} 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.",

keywords = "chronic lymphocytic leukaemia, xenograft, clonal evolution, multiplexed-FISH, cytogenetics",

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

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Davies, N, Kwok, M, Gould, C, Oldreive, C, Mao, J, Parry, H, Smith, E, Agathanggelou, A, Pratt, G, Taylor, M , Moss, P, Griffiths, M & Stankovic, T 2017, 'Dynamic changes in clonal cytogenetic architecture during progression of chronic lymphocytic leukemia in patients and patient-derived murine xenografts', OncoTarget, vol. 8, no. 27, pp. 44749-44760. https://doi.org/10.18632/oncotarget.17432

TY - JOUR

T1 - Dynamic changes in clonal cytogenetic architecture during progression of chronic lymphocytic leukemia in patients and patient-derived murine xenografts

AU - Davies, Nicholas

AU - Kwok, Marwan

AU - Gould, Clive

AU - Oldreive, Ceri

AU - Mao, Jingwen

AU - Parry, Helen

AU - Smith, Edward

AU - Agathanggelou, Angelo

AU - Pratt, Guy

AU - Taylor, Malcolm

AU - Moss, Paul

AU - Griffiths, Mike

AU - Stankovic, Tatjana

PY - 2017/4/26

Y1 - 2017/4/26

N2 - 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.

AB - 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.

KW - chronic lymphocytic leukaemia

KW - xenograft

KW - clonal evolution

KW - multiplexed-FISH

KW - cytogenetics

U2 - 10.18632/oncotarget.17432

DO - 10.18632/oncotarget.17432

M3 - Article

C2 - 28496009

SN - 1949-2553

VL - 8

SP - 44749

EP - 44760

JO - OncoTarget

JF - OncoTarget

IS - 27

ER -

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

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