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Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type diffuse large B-cell lymphoma

Bewicke-Copley, Findlay; Korfi, Koorosh; Araf, Shamza; Hodkinson, Brendan; Kumar, Emil; Cummin, Thomas; Ashton-Key, Margaret; ... Fitzgibbon, Jude; + view all (2023) Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type diffuse large B-cell lymphoma. Blood Advances , 7 (5) pp. 845-855. 10.1182/bloodadvances.2022007536. Green open access

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Abstract

Despite the effectiveness of immuno-chemotherapy, 40% of patients with diffuse large B-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 focused attention on the changes in GEP accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo patients with DLBCL. COO remained stable from diagnosis to relapse in 80% of patients, with only a single patient showing COO switching from activated B-cell–like (ABC) to germinal center B-cell–like (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 <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.

Type: Article
Title: Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type diffuse large B-cell lymphoma
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1182/bloodadvances.2022007536
Publisher version: https://doi.org/10.1182/bloodadvances.2022007536
Language: English
Additional information: © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, non-derivative use with attribution. All other rights reserved. http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Lymphoid Neoplasia
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10165037
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