Clinical impact generated by the research includes incorporation of IGHV stereotype subtype 2 and next-generation sequencing (NGS) testing for TP53 mutation by into routine CLL stratification, while whole-genome sequencing (WGS) is being considered for inclusion in the NHS Cancer Test Directory. Scientific impact includes mapping the genomic landscape in CLL, elucidating novel mechanisms of mutagenesis, synthetic lethality and drug resistance and demonstrating the feasibility and value of new technologies in primary patient samples.
Omics datasets
Omics datasets derived from the stored samples have been deposited in several publicly available data repositories including the Genomics England Trusted Research Environment (WGS data), NCBI Sequence Read Archive (TP53 ultradeep sequencing data) and the Proteome Xchange Consortium (whole proteome and kinome data). Further details are given in the section on data visualisation and analysis.
Publications
The following publications were reported by biobank users via a survey conducted in August 2022:
Identification of biologically and clinically distinct subgroups of chronic lymphocytic leukaemia from whole genome sequencing. Pauline Robbe*, Kate Ridout*, Dimitrios V. Vavoulis, Ben Kinnersley, Doriane Cavalieri, Daniel Chubb, Niamh Appleby, Alex J Cornish, Laura Lopez Pascua, Ruth Clifford, Adam Burns, Basile Stamatopoulos, Maite Cabes, Reem Alsolami, Pavlos Antoniou, Melanie Oates, Jane Gibson, Genomics England Research Consortium, Helene Dréau, Piero Carninci, Samantha JL Knight, Robert Månsson, José I Martín-Subero, Mark Ross, David Bentley, Jonathan C Strefford, Stephen Devereux, Andrew Pettitt, Peter Hillmen, Mark J Caulfield, Richard S Houlston and Anna Schuh. Nature Cancer; Manuscript in preparation.
Genomic and transcriptomic correlates of Richter's transformation in Chronic Lymphocytic Leukemia. Klintman J, Appleby N, Stamatopoulos B, Ridout K, Eyre TA, Robbe P, Lopez Pascua L, Knight SJ, Dreau HM, Cabes M, Popitsch N, Ehinger M, Martin-Subero I, Campo E, Mansson R, Rossi D, Taylor JC, Vavoulis DV, Schuh A. Blood. 2020 Nov 18: Online ahead of print. PMID: 33206936
Telomere length predicts for outcome to FCR chemotherapy in CLL. Norris K, Hillmen P, Rawstron A, Hills R, Baird DM, Fegan CD, Pepper C. Leukemia. 2019 Aug;33(8):1953-1963. doi: blood.2020005650. 10.1038/s41375-019-0389-9. Epub 2019 Jan 30. PMID: 30700843
Telomere fusions associate with coding sequence and copy number alterations in CLL. Escudero L, Cleal K, Ashelford K, Fegan C, Pepper C, Liddiard K, Baird DM.Leukemia. 2019 Aug;33(8):2093-2097. doi: 10.1038/s41375-019-0423-y. Epub 2019 Feb 22. PMID: 30796307
Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: results from 3 UK clinical trials. Wojdacz TK, Amarasinghe HE, Kadalayil L, Beattie A, Forster J, Blakemore SJ, Parker H, Bryant D, Larrayoz M, Clifford R, Robbe P, Davis ZA, Else M, Howard DR, Stamatopoulos B, Steele AJ, Rosenquist R, Collins A, Pettitt AR, H illmen P, Plass C, Schuh A, Catovsky D, Oscier DG, Rose-Zerilli MJJ, Oakes CC, Strefford JC. Blood Adv. 2019 Aug 27;3(16):2474-2481. doi: 10.1182/bloodadvances.2019000237. PMID: 31434681
An increased fraction of circulating miR-363 and miR-16 is particle bound in patients with chronic lymphocytic leukaemia as compared to normal subjects. Alharthi A, Beck D, Howard DR, Hillmen P, Oates M, Pettitt A, Wagner SD. BMC Res Notes. 2018 May 8;11(1):280. doi: 10.1186/s13104-018-3391-9
EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia. Young E, Noerenberg D, Mansouri L, Ljungström V, Frick M, Sutton LA, Blakemore SJ, Galan-Sousa J, Plevova K, Baliakas P, Rossi D, Clifford R, Roos-Weil D, Navrkalova V, Dörken B, Schmitt CA, Smedby KE, Juliusson G, Giacopelli B, Blachly JS, Belessi C, Panagiotidis P, Chiorazzi N, Davi F, Langerak AW, Oscier D, Schuh A, Gaidano G, Ghia P, Xu W, Fan L, Bernard OA, Nguyen-Khac F, Rassenti L, Li J, Kipps TJ, Stamatopoulos K, Pospisilova S, Zenz T, Oakes CC, Strefford JC, Rosenquist R, Damm F. Leukemia. 2017 Jul;31(7):1547-1554. doi: 10.1038/leu.2016.359
Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia. Parker H, Rose-Zerilli MJ, Larrayoz M, Clifford R, Edelmann J, Blakemore S, Gibson J, Wang J, Ljungström V, Wojdacz TK, Chaplin T, Roghanian A, Davis Z, Parker A, Tausch E, Ntoufa S, Ramos S, Robbe P, Alsolami R, Steele AJ, Packham G, Rodríguez-Vicente AE, Brown L, McNicholl F, Forconi F, Pettitt A, Hillmen P, Dyer M, Cragg MS, Chelala C, Oakes CC, Rosenquist R, Stamatopoulos K, Stilgenbauer S, Knight S, Schuh A, Oscier DG, Strefford JC. Leukemia. 2016 Nov;30(11):2179-2186. doi: 10.1038/leu.2016.134
NCRI phase II study of CHOP in combination with ofatumumab in induction and maintenance in newly diagnosed Richter syndrome. Eyre TA, Clifford R, Bloor A, Boyle L, Roberts C, Cabes M, Collins GP, Devereux S, Follows G, Fox CP, Gribben J, Hillmen P, Hatton CS, Littlewood TJ, McCarthy H, Murray J, Pettitt AR, Soilleux E, Stamatopoulos B, Love SB, Wotherspoon A, Schuh A. Br J Haematol. 2016 Oct;175(1):43-54. doi: 10.1111/bjh.14177
Diagnostic dilemmas of high-grade transformation (Richter's syndrome) of chronic lymphocytic leukaemia: Results of the phase II National Cancer Research Institute CHOP-OR clinical trial specialist haemato-pathology central review. Soilleux, E. J. Wotherspoon A, Eyre TA, Clifford R, Cabes M, Schuh A. Histopathology. 2016 Dec;69(6):1066-1076. doi: 10.1111/his.13024. PMID:27345622
Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations. Ljungström V, Cortese D, Young E, Pandzic T, Mansouri L, Plevova K, Ntoufa S, Baliakas P, Clifford R, Sutton LA, Blakemore SJ, Stavroyianni N, Agathangelidis A, Rossi D, Höglund M, Kotaskova J, Juliusson G, Belessi C, Chiorazzi N, Panagiotidis P, Langerak AW, Smedby KE, Oscier D, Gaidano G, Schuh A, Davi F, Pott C, Strefford JC, Trentin L, Pospisilova S, Ghia P, Stamatopoulos K, Sjöblom T, Rosenquist R. Blood. 2016 Feb 25;127(8):1007-16. doi: 10.1182/blood-2015-10-674572
SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage. Clifford R, Louis T, Robbe P, Ackroyd S, Burns A, Timbs AT, Wright Colopy G, Dreau H, Sigaux F, Judde JG, Rotger M, Telenti A, Lin YL, Pasero P, Maelfait J, Titsias M, Cohen DR, Henderson SJ, Ross MT, Bentley D, Hillmen P, Pettitt A, Rehwinkel J, Knight SJ, Taylor JC, Crow YJ, Benkirane M, Schuh A. Blood. 2014 Feb 13;123(7):1021-31. doi: 10.1182/blood-2013-04-490847
Combined analysis of IGHV mutations, telomere length and CD49d identifies long-term progression-free survivors in TP53 wild-type CLL treated with FCR-based therapies. Pepper AGS, Zucchetto A, Norris K, Tissino E, Polesel J, Soe Z, Allsup D, Hockaday A, Ow PL, Hillmen P, Rawstron A, Catovsky D, Bulian P, Bomben R, Baird DM, Fegan CD, Gattei V, Pepper C. Leukemia. 2022 Jan;36(1):271-274. doi: 10.1038/s41375-021-01322-1. Epub 2021 Jun 19. PMID: 34148055 Free PMC article. No abstract available.
Long-term follow-up of 415 patients with chronic lymphocytic leukemia treated with fludarabine and cyclophosphamide-based chemoimmunotherapy in the frontline ADMIRE and ARCTIC trials: A comprehensive assessment of prognostic factors. Allsup DJ, Craig Z, Cairns D, Howard D, Hockaday A, Bloor A, Soe Z, Pepper C, Gattei V, Zucchetto A, Robbe P, Clifford R, Schuh A, Munir T, Rawstron A, Hillmen P. Am J Hematol. 2022 Feb 2. doi: 10.1002/ajh.26483. Online ahead of print. PMID: 35108412 No abstract available.
TP53 Mutations with Low Variant Allele Frequency Predict Short Survival in Chronic Lymphocytic Leukemia. Bomben R, Rossi FM, Vit F, Bittolo T, D'Agaro T, Zucchetto A, Tissino E, Pozzo F, Vendramini E, Degan M, Zaina E, Cattarossi I, Varaschin P, Nanni P, Berton M, Braida A, Polesel J, Cohen JA, Santinelli E, Biagi A, Gentile M, Morabito F, Fronza G, Pozzato G, D'Arena G, Olivieri J, Bulian P, Pepper C, Hockaday A, Schuh A, Hillmen P, Rossi D, Chiarenza A, Zaja F, Di Raimondo F, Del Poeta G, Gattei V. Clin Cancer Res. 2021 Oct 15;27(20):5566-5575. doi: 10.1158/1078-0432.CCR-21-0701. Epub 2021 Jul 20. PMID: 34285062
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