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Article Dans Une Revue Blood Advances Année : 2022

Genomic and microenvironmental landscape of stage I follicular lymphoma, compared with stage III/IV

G. Tjitske Los-de Vries
Wendy Stevens
Erik van Dijk
Carole Langois-Jacques
  • Fonction : Auteur
Andrew Clear
Phylicia Stathi
Margaretha Roemer
Matias Mendeville
Nathalie Hijmering
  • Fonction : Auteur
Birgitta Sander
  • Fonction : Auteur
Andreas Rosenwald
  • Fonction : Auteur
Maria Calaminici
  • Fonction : Auteur
Eva Hoster
Wolfgang Hiddemann
  • Fonction : Auteur
Philippe Gaulard
  • Fonction : Auteur
Gilles Salles
Heike Horn
  • Fonction : Auteur
Wolfram Klapper
Luc Xerri
  • Fonction : Auteur
Catherine Burton
  • Fonction : Auteur
Reuben Tooze
Alexandra Smith
  • Fonction : Auteur
Christian Buske
  • Fonction : Auteur
David Scott
Yasodha Natkunam
  • Fonction : Auteur
Ranjana Advani
  • Fonction : Auteur
Laurie Sehn
  • Fonction : Auteur
John Raemaekers
  • Fonction : Auteur
John Gribben
Eva Kimby
  • Fonction : Auteur
Marie José Kersten
  • Fonction : Auteur
Bauke Ylstra
Daphne de Jong

Résumé

Abstract Although the genomic and immune microenvironmental landscape of follicular lymphoma (FL) has been extensively investigated, little is known about the potential biological differences between stage I and stage III/IV disease. Using next-generation sequencing and immunohistochemistry, 82 FL nodal stage I cases were analyzed and compared with 139 FL stage III/IV nodal cases. Many similarities in mutations, chromosomal copy number aberrations, and microenvironmental cell populations were detected. However, there were also significant differences in microenvironmental and genomic features. CD8+ T cells (P = .02) and STAT6 mutations (false discovery rate [FDR] <0.001) were more frequent in stage I FL. In contrast, programmed cell death protein 1–positive T cells, CD68+/CD163+ macrophages (P < .001), BCL2 translocation (BCL2trl+) (P < .0001), and KMT2D (FDR = 0.003) and CREBBP (FDR = 0.04) mutations were found more frequently in stage III/IV FL. Using clustering, we identified 3 clusters within stage I, and 2 clusters within stage III/IV. The BLC2trl+ stage I cluster was comparable to the BCL2trl+ cluster in stage III/IV. The two BCL2trl– stage I clusters were unique for stage I. One was enriched for CREBBP (95%) and STAT6 (64%) mutations, without BLC6 translocation (BCL6trl), whereas the BCL2trl– stage III/IV cluster contained BCL6trl (64%) with fewer CREBBP (45%) and STAT6 (9%) mutations. The other BCL2trl– stage I cluster was relatively heterogeneous with more copy number aberrations and linker histone mutations. This exploratory study shows that stage I FL is genetically heterogeneous with different underlying oncogenic pathways. Stage I FL BCL2trl– is likely STAT6 driven, whereas BCL2trl– stage III/IV appears to be more BCL6trl driven.

Dates et versions

hal-04150930 , version 1 (04-07-2023)

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Citer

G. Tjitske Los-de Vries, Wendy Stevens, Erik van Dijk, Carole Langois-Jacques, Andrew Clear, et al.. Genomic and microenvironmental landscape of stage I follicular lymphoma, compared with stage III/IV. Blood Advances, 2022, 6 (18), pp.5482-5493. ⟨10.1182/bloodadvances.2022008355⟩. ⟨hal-04150930⟩

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