Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type Diffuse Large B Cell Lymphoma

Findlay Bewicke-Copley, Koorosh Korfi, Shamza Araf, Brendan Hodkinson, Emil Kumar, Thomas Cummin, Margaret Ashton-Key, Sharon L Barrans, Suzan JL van Hoppe, Cathy Burton, Mohamed Elshiekh, Simon Rule, Nicola Crosbie, Andrew James Clear, Maria Calaminici, Hendrik Friedrich Peter Runge, Robert K Hills, David W. Scott, Lisa M Rimsza, Geetha MenonChulin Sha, John Davies, Ai Nagano, Andrew John Davies, Daniel Painter, Alexandra Smith, John G Gribben, Kikkeri N Naresh, David Robert Westhead, Jessica Okosun, Andrew J Steele, Daniel J Hodson, Sriram Balasubramanian, Peter W. M. Johnson, Jun Wang, Jude Fitzgibbon

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Despite the effectiveness of immuno-chemotherapy, 40\cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but fell short of providing a consistent relapse-specific genetic signature. In our study, we have focussed attention on the changes in gene expression profile accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo DLBCL patients. Cell of origin remained stable from diagnosis to relapse in 80\ with only a single patient showing COO switching from ABC to GCB. Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC-DLBCLs derived from relapse-associated genes, that defined clinically distinct high and low risk subgroups in ABC-DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of \lt;60-year-old patients with superior PFS and OS treated with Ibrutinib-R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials.
Original languageEnglish
JournalBlood Advances
Publication statusPublished - 10 Aug 2022

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