# Cell of origin (GCB vs ABC)

Source: https://onco.cc/terms/cell-of-origin/  
OnCo record `cell-of-origin` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Whether a large B-cell lymphoma resembles a germinal-centre B cell or an activated B cell; the activated type does worse and depends on different pathways.

## Summary

Cell of origin classifies diffuse large B-cell lymphoma by whether it resembles a germinal-centre B cell (GCB) or an activated B cell (ABC); the activated type does worse and depends on different pathways. It is determined by gene expression with the Lymph2Cx assay or approximated by the Hans immunohistochemistry algorithm. ABC or non-GCB lymphomas depend on NF-kappaB and B-cell receptor signalling through BTK, IRAK4 and MYD88 L265P, while GCB lymphomas depend on BCL-2 and EZH2; the CD79b target entry also links here. Newer genetic classifications such as LymphGen, with its MCD, BN2, N1, EZB, ST2 and A53 clusters, refine the split but are not yet clinically routine. The concept also appears in primary CNS lymphoma and HIV-associated lymphomas.

## Fields

- Kind: Term
- Last checked: 2026-09-07
- Also known as: Hans algorithm; Hans classifier; Hans criteria; Lymph2Cx; GCB; ABC; non-GCB; germinal centre B-cell-like; activated B-cell-like; COO; LymphGen

## Notes

- How it is called, and what it is worth. The reference method is gene expression profiling; what most laboratories report is the Hans algorithm, three stains read in order, CD10 then BCL6 then MUM1. On 152 cases with a microarray comparison, Hans called 42% germinal-centre and 58% non-germinal-centre, with five-year overall survival of 76% against 34% (Hans 2004). Because immunohistochemistry cannot separate the activated type from the unclassified type, a careful report says germinal-centre or non-germinal-centre. The split was first found by microarray (Alizadeh 2000) and confirmed on 240 patients, where BCL2 translocation and c-REL amplification occurred only in the germinal-centre group (Rosenwald 2002). What it changes today is small and should be said plainly: it is prognostic, it decides trial eligibility, and no licensed regimen is chosen by it.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Diffuse_large_B-cell_lymphoma
- Distinct types of DLBCL by gene expression profiling (Alizadeh et al., Nature 2000): https://doi.org/10.1038/35000501
- Hans et al., Blood 2004: the CD10, BCL6 and MUM1 immunohistochemistry algorithm on 152 cases: https://doi.org/10.1182/blood-2003-05-1545
- Alizadeh et al., Nature 2000: distinct types of diffuse large B-cell lymphoma identified by gene expression profiling: https://doi.org/10.1038/35000501
- Rosenwald et al., N Engl J Med 2002: molecular profiling predicts survival after chemotherapy in 240 diffuse large B-cell lymphomas: https://doi.org/10.1056/NEJMoa012914

## Connected records

- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [HIV-associated (AIDS-related) lymphomas](https://onco.cc/cancers/hiv-associated-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Primary CNS lymphoma](https://onco.cc/cancers/primary-cns-lymphoma/)
- targets: [BCL-2](https://onco.cc/targets/bcl2/), [CD79b](https://onco.cc/targets/cd79b/), [CREBBP](https://onco.cc/targets/crebbp/), [EZH2](https://onco.cc/targets/ezh2/), [MYD88](https://onco.cc/targets/myd88/)
- terms: [Cell of origin in practice: Hans against expression profiling, and what it changes](https://onco.cc/terms/lymphoma-bio-cell-of-origin-in-practice/), [LymphGen and the genetic clusters of large B-cell lymphoma](https://onco.cc/terms/lymphoma-bio-lymphgen/), [MYD88 L265P and CXCR4 mutations](https://onco.cc/terms/myd88-l265p/), [The germinal centre: why lymphoma starts where antibodies are made](https://onco.cc/terms/lymphoma-bio-germinal-centre/)
- key papers: [A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications](https://onco.cc/key-papers/paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020/), [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 biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumour DNA](https://onco.cc/key-papers/paper-scherer-ctdna-lymphoma-subtypes-genome-evolution-sci-transl-med-2016/), [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/), [Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes](https://onco.cc/key-papers/paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018/), [Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma](https://onco.cc/key-papers/paper-goya-obinutuzumab-vs-rituximab-chop-dlbcl-jco-2017/), [Randomized phase III trial of ibrutinib and R-CHOP in non-germinal centre B-cell diffuse large B-cell lymphoma (PHOENIX)](https://onco.cc/key-papers/paper-phoenix-ibrutinib-r-chop-non-gcb-dlbcl-jco-2019/), [The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma](https://onco.cc/key-papers/paper-rosenwald-molecular-profiling-dlbcl-nejm-2002/)
- pathways: [The germinal centre reaction](https://onco.cc/pathways/germinal-centre-reaction/)
- biomarkers: [CD79B ITAM mutation](https://onco.cc/biomarkers/cd79b-itam-mutation/), [Double expressor: MYC and BCL2 protein together by immunohistochemistry](https://onco.cc/biomarkers/myc-bcl2-double-expressor/)
- trials: [ARCHED](https://onco.cc/trials/arched/), [GOYA](https://onco.cc/trials/goya/)
- 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/)
- ideas: [Assign first-line treatment in diffuse large B-cell lymphoma by genetic subtype, not by a three-antibody stain](https://onco.cc/ideas/lymphoma-ev-genetic-subtype-directed-first-line/)

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