# The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma

Source: https://onco.cc/key-papers/paper-rosenwald-molecular-profiling-dlbcl-nejm-2002/  
OnCo record `paper-rosenwald-molecular-profiling-dlbcl-nejm-2002` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Reading which genes were switched on in 240 lymphoma samples sorted one disease into three, and the group whose cells looked like a particular stage of normal B-cell development lived the longest.

## Summary

Alizadeh and Staudt had shown in 2000 that diffuse large B-cell lymphoma is not one disease. Rosenwald and the Lymphoma/Leukemia Molecular Profiling Project turned that into a survival predictor. Biopsy samples from 240 patients were profiled on DNA microarrays and analysed for genomic abnormalities; subgroups were defined by hierarchical clustering, and a risk predictor was built on 160 patients and tested on the remaining 80.

Three gene-expression subgroups came out: germinal-centre B-cell-like, activated B-cell-like, and type 3. The two commonest oncogenic events in the disease, the BCL2 translocation and c-rel amplification, were found only in the germinal-centre group, which also had the highest five-year survival. Searching for individual genes whose expression tracked survival produced four signatures, reflecting germinal-centre B cells, proliferating cells, the reactive stromal and immune cells of the lymph node, and the major histocompatibility complex class II complex. Seventeen of those genes were assembled into a predictor of overall survival after chemotherapy, which was independent of the International Prognostic Index.

The stromal and immune signatures are the part that aged best: they anticipated by a decade the idea that what surrounds the tumour predicts outcome as strongly as what is in it.

## Fields

- Kind: Key paper
- Last checked: 2026-10-01
- Also known as: Rosenwald 2002; Lymphoma/Leukemia Molecular Profiling Project 240 biopsies; Germinal-centre, activated and type 3 diffuse large B-cell lymphoma
- Tags: lymphoma-evidence
- Journal: New England Journal of Medicine
- Year: 2002
- DOI: 10.1056/NEJMoa012914
- Authors: Rosenwald A, Wright G, Chan WC, et al.
- Findings: Three gene-expression subgroups were identified in diffuse large B-cell lymphoma: germinal-centre B-cell-like, activated B-cell-like, and type 3.; The BCL2 translocation and c-rel amplification were detected only in the germinal-centre B-cell-like subgroup, which had the highest five-year survival rate.; Genes whose expression correlated with survival fell into four signatures: germinal-centre B cell, proliferation, lymph-node reactive stromal and immune cells, and major histocompatibility complex class II.; A 17-gene predictor of overall survival after chemotherapy was constructed on 160 patients and validated on 80, and was prognostic independently of the International Prognostic Index.
- What it means: The reason a pathology report on diffuse large B-cell lymphoma says germinal-centre or non-germinal-centre, and the origin of every attempt since to treat the two differently. It also made the case that microarray profiling could do something the clinical index could not, which is what pulled genomics into haematology.
- Caveats: The predictor was built in the era before rituximab; adding rituximab narrowed, though it did not erase, the survival gap between the subgroups.; Type 3 was a residual category rather than a biological entity and has not survived as a classification.; Microarray profiling on fresh-frozen tissue was never routinely available; the Hans immunohistochemistry algorithm was the compromise that carried the idea into clinics, at the cost of accuracy.

## Sources

- New England Journal of Medicine 2002: https://doi.org/10.1056/NEJMoa012914
- PubMed: https://pubmed.ncbi.nlm.nih.gov/12075054/
- Europe PMC: https://europepmc.org/article/MED/12075054

## Connected records

- key papers: [Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray](https://onco.cc/key-papers/paper-hans-immunohistochemistry-cell-of-origin-dlbcl-blood-2004/), [Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling](https://onco.cc/key-papers/paper-alizadeh-nature/), [Genetics and pathogenesis of diffuse large B-cell lymphoma](https://onco.cc/key-papers/paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018/)
- roadmaps: [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/)
- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- fronts: [AI & Computation](https://onco.cc/fronts/ai-computation/), [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/)
- targets: [BCL-2](https://onco.cc/targets/bcl2/), [BCL6](https://onco.cc/targets/bcl6/)
- pathways: [MYC](https://onco.cc/pathways/myc/)
- institutions: [National Cancer Institute (NIH)](https://onco.cc/institutions/nci/)
- terms: [Cell of origin (GCB vs ABC)](https://onco.cc/terms/cell-of-origin/), [International Prognostic Index (IPI)](https://onco.cc/terms/ipi-score/)
- people: [Louis M. Staudt](https://onco.cc/people/louis-staudt/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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