Relationship between BCL2 mutations and follicular lymphoma outcome in the chemoimmunotherapy era.
Journal
Blood cancer journal
ISSN: 2044-5385
Titre abrégé: Blood Cancer J
Pays: United States
ID NLM: 101568469
Informations de publication
Date de publication:
17 05 2023
17 05 2023
Historique:
received:
23
11
2022
accepted:
27
04
2023
revised:
21
04
2023
medline:
18
5
2023
pubmed:
17
5
2023
entrez:
16
5
2023
Statut:
epublish
Résumé
How to identify follicular lymphoma (FL) patients with low disease burden but high risk for early progression is unclear. Building on a prior study demonstrating the early transformation of FLs with high variant allele frequency (VAF) BCL2 mutations at activation-induced cytidine deaminase (AICDA) sites, we examined 11 AICDA mutational targets, including BCL2, BCL6, PAX5, PIM1, RHOH, SOCS, and MYC, in 199 newly diagnosed grade 1 and 2 FLs. BCL2 mutations with VAF ≥20% occurred in 52% of cases. Among 97 FL patients who did not initially receive rituximab-containing therapy, nonsynonymous BCL2 mutations at VAF ≥20% were associated with increased transformation risk (HR 3.01, 95% CI 1.04-8.78, p = 0.043) and a trend toward shorter event-free survival (EFS, median 20 months with mutations versus 54 months without, p = 0.052). Other sequenced genes were less frequently mutated and did not increase the prognostic value of the panel. Across the entire population, nonsynonymous BCL2 mutations at VAF ≥20% were associated with decreased EFS (HR 1.55, 95% CI 1.02-2.35, p = 0.043 after correction for FLIPI and treatment) and decreased overall survival after median 14-year follow-up (HR 1.82, 95% CI 1.05-3.17, p = 0.034). Thus, high VAF nonsynonymous BCL2 mutations remain prognostic even in the chemoimmunotherapy era.
Identifiants
pubmed: 37193683
doi: 10.1038/s41408-023-00847-1
pii: 10.1038/s41408-023-00847-1
pmc: PMC10188323
doi:
Substances chimiques
Proto-Oncogene Proteins c-bcl-2
0
BCL2 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
81Subventions
Organisme : NCI NIH HHS
ID : P30 CA015083
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA195568
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA097274
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA116642
Pays : United States
Informations de copyright
© 2023. The Author(s).
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