Abstract:
: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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Lin WY,Fordham SE,Sunter N,Elstob C,Rahman T,Willmore E,Shepherd C,Strathdee G,Mainou-Fowler T,Piddock R,Mearns H,Barrow T,Houlston RS,Marr H,Wallis J,Summerfield G,Marshall S,Pettitt A,Pepper C,Fegan C,Forconi Fdoi
10.1038/s41467-020-20822-9subject
Has Abstractpub_date
2021-01-28 00:00:00pages
665issue
1issn
2041-1723pii
10.1038/s41467-020-20822-9journal_volume
12pub_type
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