Home / Research / Transformation to DLBCL
Some follicular lymphomas transform into an aggressive lymphoma, most often diffuse large B-cell lymphoma. These papers trace how that happens: which clones expand, which mutations are gained, how the microenvironment changes, and how often transformation occurs.
Not medical advice. These are short, plain-English summaries of published research, written for education. They are not treatment recommendations. Questions about an individual situation belong with a hematologist or oncologist.
Haradhvala NJ, Yiu SPT, et al. Cancer Discov. 2026.
Multimodal profiling of 95 FL and transformed FL samples, including single-cell, spatial and protein data, found that transformation involves expansion of fibroblasts and GPNMB-positive macrophages and loss of the stromal cells that organize the lymph node. These changes altered cytokine patterns that affect T cells and macrophages, and some of the signals were detectable in blood plasma.
Parry EM, Okosun J Blood. 2025.
This review summarizes current knowledge of how FL transforms, including the additional genetic changes, newly active signaling pathways and origin from an ancestral FL clone. It discusses risk prediction, memory-like B-cell phenotypes, tumor and immune interactions and the changing treatment landscape, and proposes priorities for future research.
Fernández-Miranda I, Pedrosa L, et al. Mod Pathol. 2024.
Combining mutation data with the clinical FLIPI score, the authors built a model using HIST1H1E, KMT2D and TNFRSF14 status to estimate transformation risk at diagnosis. The model reached a concordance index of 0.746 in the development cohort and was also tested in an external validation cohort (0.552), laying groundwork for genetic risk tools that later studies continue to refine.
Sarkozy C, Wu S, et al. Cancer Cell. 2024.
Single-cell genome and transcriptome sequencing of 11 paired samples from before and after transformation showed malignant B cells and their microenvironment changing together, with an emerging immune exhaustion signature. The findings were turned into a microenvironment-based transformation biomarker that was validated in two independent pretreatment cohorts.
Wang X, Nissen M, et al. Nat Commun. 2022.
Mass cytometry of 155 diagnostic FL biopsies found two recurrent tumor patterns, one resembling germinal center B cells and one resembling memory B cells. The memory B-cell-like pattern and greater diversity of cell phenotypes within a tumor were each independently associated with higher transformation risk.
Federico M, Caballero Barrigón MD, et al. Lancet Haematol. 2018.
This pooled analysis of 8,116 European patients estimated a 10-year cumulative hazard of histologic transformation of 7.7%. Transformation risk was lower in patients who had received rituximab, while survival after transformation did not differ by prior rituximab exposure.
Kridel R, Chan FC, et al. PLoS Med. 2016.
Tracking clones in matched diagnostic and later samples, this study found that transformed tumors were usually dominated by clones that were rare or undetectable at diagnosis, whereas early progression arose from clones already present. Mutations in genes such as TP53, B2M and CCND3 were more common at transformation, suggesting the two events follow different evolutionary paths.
Wagner-Johnston ND, Link BK, et al. Blood. 2015.
Among 2,652 patients in the prospective US National LymphoCare Study, 14.3% transformed over a median follow-up of 6.8 years. Several features at diagnosis were associated with transformation risk, and median overall survival after transformation was 5 years.
Pasqualucci L, Khiabanian H, et al. Cell Rep. 2014.
Exome sequencing and copy-number analysis showed that FL and transformed FL evolve divergently from a common mutated precursor. Transformation was specifically linked to alterations in cell-cycle and DNA damage genes (CDKN2A/B, MYC and TP53) and to aberrant somatic hypermutation.
Okosun J, Bödör C, et al. Nat Genet. 2014.
Sequencing paired follicular and transformed lymphoma samples showed that both arise from a common progenitor clone. Mutations in chromatin regulators such as CREBBP, EZH2 and KMT2D occurred early, while changes in EBF1 and NF-kB regulators such as MYD88 and TNFAIP3 were gained at transformation.
10 papers, newest first. Titles, authors, journals, years and DOIs were checked against PubMed on 2026-10-20. Back to the Research library.