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Relapses in early-stage follicular lymphoma frequently develop via a divergent evolution from their clonally related precursor cells.

Accepted version
Peer-reviewed

Type

Article

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Authors

Wotherspoon, Andrew 
Tzioni, Maria-Myrsini 
Chen, Zi 
Guo, Sarah 

Abstract

Follicular lymphoma (FL) develops through a stepwise acquisition of cooperative genetic changes with t(14;18)(q32;q21)/IGH::BCL2 occurring early at the pre-B stage of B-cell development. Patients with FL typically show an indolent clinical course, remitting and relapsing with the eventual development of resistance to treatments. Interestingly, the majority of transformed FL do not progress directly from FL but originate from their clonally related lymphoma precursor (CLP) cells. To examine whether such divergent tumour evolution also underpins the relapses in patients with early-stage FL, we investigated by targeted next-generation sequencing 13 cases (stage I = 9, stage II = 4), who showed complete remission (mean: 5 years; range: 1-11.5 years) following local radiotherapy but subsequently relapsed (≥2 in 5). A clonal relationship between the diagnostic FL and relapses was confirmed in 11 cases. In six cases, common and distinct variants were seen between the paired diagnostic and relapsed lymphomas, indicating their divergent evolution from a CLP. In two cases, different B-cell clones were involved in the diagnostic and relapsed lymphomas, including one case involving two different BCL2 translocations. In the remaining five cases, the relapsed lymphoma developed via a linear progression (n = 4) or a mixed evolutionary path (n = 1). These findings may bear important implications in the routine diagnosis and management of relapsed FL. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Description

Keywords

follicular lymphoma, lymphoma recurrence, mutation profiling, tumour evolution, Humans, Lymphoma, Follicular, Neoplasm Recurrence, Local, Translocation, Genetic, Proto-Oncogene Proteins c-bcl-2, United Kingdom

Journal Title

J Pathol

Conference Name

Journal ISSN

0022-3417
1096-9896

Volume Title

Publisher

Pathological Society of Great Britain and Ireland
Sponsorship
Bloodwise (via University of Southampton) (19011 519781101)
Blood Cancer UK (19010)
Cancer Research UK (C8333/A29707)
Biotechnology and Biological Sciences Research Council (BB/M011194/1)
Blood Cancer UK