Wei Yu Lin
Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia
Lin, Wei Yu; Fordham, Sarah E.; Sunter, Nicola; Elstob, Claire; Rahman, Thahira; Willmore, Elaine; Shepherd, Colin; Strathdee, Gordon; Mainou-Fowler, Tryfonia; Piddock, Rachel; Mearns, Hannah; Barrow, Timothy; Houlston, Richard S.; Marr, Helen; Wallis, Jonathan; Summerfield, Geoffrey; Marshall, Scott; Pettitt, Andrew; Pepper, Christopher; Fegan, Christopher; Forconi, Francesco; Dyer, Martin J.S.; Jayne, Sandrine; Sellors, April; Schuh, Anna; Robbe, Pauline; Oscier, David; Bailey, James; Rais, Syed; Bentley, Alison; Cawkwell, Lynn; Evans, Paul; Hillmen, Peter; Pratt, Guy; Allsup, David J.; Allan, James M.
Sarah E. Fordham
Richard S. Houlston
Martin J.S. Dyer
Dr David Allsup D.J.Allsup@hull.ac.uk
Senior Lecturer in Haematology and Honorary Consultant
James M. Allan
© 2021, The Author(s). Prognostication in patients with chronic lymphocytic leukemia (CLL) is challenging due to heterogeneity in clinical course. We hypothesize that constitutional genetic variation affects disease progression and could aid prognostication. Pooling data from seven studies incorporating 842 cases identifies two genomic locations associated with time from diagnosis to treatment, including 10q26.13 (rs736456, hazard ratio (HR) = 1.78, 95% confidence interval (CI) = 1.47–2.15; P = 2.71 × 10−9) and 6p (rs3778076, HR = 1.99, 95% CI = 1.55–2.55; P = 5.08 × 10−8), which are particularly powerful prognostic markers in patients with early stage CLL otherwise characterized by low-risk features. Expression quantitative trait loci analysis identifies putative functional genes implicated in modulating B-cell receptor or innate immune responses, key pathways in CLL pathogenesis. In this work we identify rs736456 and rs3778076 as prognostic in CLL, demonstrating that disease progression is determined by constitutional genetic variation as well as known somatic drivers.
Lin, W. Y., Fordham, S. E., Sunter, N., Elstob, C., Rahman, T., Willmore, E., …Allan, J. M. (2021). Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia. Nature communications, 12(1), Article 665. https://doi.org/10.1038/s41467-020-20822-9
|Journal Article Type||Article|
|Acceptance Date||Dec 16, 2020|
|Online Publication Date||Jan 28, 2021|
|Deposit Date||Jan 28, 2021|
|Publicly Available Date||Oct 27, 2022|
|Publisher||Nature Publishing Group|
|Peer Reviewed||Peer Reviewed|
|Keywords||Cancer genetics; Cancer genomics; Chronic lymphocytic leukaemia; Genetic markers; Prognostic markers|
© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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