# High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma)

Source: https://onco.cc/cancers/high-grade-b-cell-lymphoma-myc-bcl2/  
OnCo record `high-grade-b-cell-lymphoma-myc-bcl2` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An aggressive B-cell lymphoma defined not by how it looks but by two genetic faults in the same cell: a rearrangement of MYC, which drives growth, and one of BCL2, which blocks the cell from dying. It behaves worse than ordinary diffuse large B-cell lymphoma, so finding the rearrangements changes the treatment.

## Summary

What it is. Two genes have to be broken for this diagnosis. MYC is a master switch for cell growth; BCL2 is the brake on programmed cell death. A cell that is told to grow and is also prevented from dying becomes a lymphoma that behaves worse than either fault alone would predict. The rearrangements are found by fluorescence in situ hybridisation, a test done on the biopsy, and they are the diagnosis. Nothing about the way the cells look under a microscope reliably identifies them, which is why every aggressive B-cell lymphoma is now tested.

How it differs from its family. It is a separate entity from diffuse large B-cell lymphoma, although it was carved out of it. WHO-HAEM5 named it diffuse large B-cell lymphoma / high-grade B-cell lymphoma with MYC and BCL2 rearrangements, so that a tumour made of large cells and one made of smaller blastoid cells can carry the same name once the genetics are known; the two books describe it as a homogeneous group with a germinal-centre gene expression profile and a close relationship to follicular lymphoma. Its gene expression overlaps that of Burkitt lymphoma, which is the other aggressive germinal-centre disease driven by MYC.

Where the two classifications disagree, and why it matters to a reader. Until 2022, cases with MYC and BCL6 rearrangements were counted in the same category. Both books removed them, because their gene expression and mutations are varied and differ from the MYC and BCL2 group. WHO-HAEM5 sends them back to diffuse large B-cell lymphoma or to high-grade B-cell lymphoma not otherwise specified, chosen on how the cells look. The International Consensus Classification created a new provisional entity for them instead, called high-grade B-cell lymphoma with MYC and BCL6 rearrangements. So a person with MYC and BCL6 rearrangements may be told they have a double-hit lymphoma by one pathologist and diffuse large B-cell lymphoma by another, and both are following a 2022 classification.

What the signature adds. The gene expression signature that characterises this entity can be present without the rearrangements. In the study that defined it, the signature was found in 27 per cent of germinal-centre diffuse large B-cell lymphomas, only half of which had the double rearrangement, and the people who carried the signature had worse outcomes after standard immunochemotherapy whether or not the rearrangements were there: a five-year time to progression of 57 per cent against 81 per cent. A commercial assay (the DLBCL90 NanoString panel) reproduced that result. The clinical implication is uncomfortable and honest: the test in daily use identifies some but not all of the biologically distinct group.

How it is treated. More intensively than diffuse large B-cell lymphoma, with prophylaxis against spread to the brain and spinal cord, which is more likely here. The regimens and the evidence for them, which is observational rather than randomised, are written on the diffuse large B-cell lymphoma page and in the treatment layer of this family.

## Fields

- Kind: Cancer
- Last checked: 2026-09-29
- Also known as: Double-hit lymphoma; DHL; HGBL-MYC/BCL2; HGBCL-DH-BCL2; Diffuse large B-cell lymphoma/high grade B-cell lymphoma with MYC and BCL2 rearrangements; High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; Double-hit B-cell lymphoma; Triple-hit lymphoma
- Tags: heme; lymphoma; subtype-page
- Group: haematologic
- Burden: No United Kingdom population figure exists under the name the 2022 classifications gave this entity, and the corpus does not invent one. What can be said is how often the genetics are found when they are looked for: in the gene-expression study that defined the double-hit signature, 25 of 157 germinal-centre diffuse large B-cell lymphomas carried rearrangements of both MYC and BCL2, and 27 per cent of the whole series carried the signature even though only half of those had the rearrangements. That cohort was assembled to contain the cases, so it is not a population frequency.
- Subtypes: Large-cell morphology, which looks like diffuse large B-cell lymphoma down the microscope; High-grade or blastoid morphology, made of medium-sized cells; With an additional BCL6 rearrangement, historically called triple-hit
- Biomarkers: MYC rearrangement and BCL2 rearrangement, both by fluorescence in situ hybridisation; the diagnosis cannot be made without them; BCL6 rearrangement, reported separately because the 2022 classifications moved MYC with BCL6 out of this entity; Germinal-centre B-cell phenotype: CD10 positive, BCL6 positive, MUM1 usually negative; The double-hit gene expression signature (DHITsig or MHG), measurable on a NanoString panel, which marks a larger group than the rearrangements do; Dual expression of MYC and BCL2 protein by immunohistochemistry, which is a different and much commoner finding and is not this entity

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/high-grade-b-cell-lymphoma-myc-bcl2/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/high-grade-b-cell-lymphoma-myc-bcl2/#overview
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/high-grade-b-cell-lymphoma-myc-bcl2/#what-it-is [3 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/high-grade-b-cell-lymphoma-myc-bcl2/#finding-it [5 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/high-grade-b-cell-lymphoma-myc-bcl2/#treating-it [2 settings]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/high-grade-b-cell-lymphoma-myc-bcl2/#evidence [3 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/high-grade-b-cell-lymphoma-myc-bcl2/#science [2 targets, 1 pathway]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/high-grade-b-cell-lymphoma-myc-bcl2/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/high-grade-b-cell-lymphoma-myc-bcl2/#living-with-it [11 questions, 4 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/high-grade-b-cell-lymphoma-myc-bcl2/coming/ [1 medicine, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/high-grade-b-cell-lymphoma-myc-bcl2/data/ [19 connected records]

## Standard of care

- Making the diagnosis: Every aggressive B-cell lymphoma biopsy is tested by fluorescence in situ hybridisation for MYC, and if MYC is rearranged, for BCL2 and BCL6. A lymphoma cannot be identified as double-hit by appearance, by immunohistochemistry for MYC and BCL2 protein, or by the cell-of-origin assay; dual protein expression is a separate and much commoner finding with its own, lesser, prognostic weight. Follicular lymphoma is excluded from the entity by both classifications even when it carries both rearrangements. ([Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [MYC](https://onco.cc/pathways/myc/), [BCL-2](https://onco.cc/targets/bcl2/), [Double-hit / high-grade B-cell lymphoma](https://onco.cc/terms/double-hit-lymphoma/), [The two lymphoma classifications of 2022 (WHO-HAEM5 and ICC)](https://onco.cc/terms/lymphoma-classification-2022/))
- Treatment, and what is known about it: Treated more intensively than diffuse large B-cell lymphoma, and with prophylaxis against disease in the brain and spinal cord, which is more frequent here. There has never been a randomised trial confined to this entity: the intensified regimens in use were adopted from retrospective comparisons after the group was shown to do less well with standard immunochemotherapy. The regimens, the doses and the evidence behind each are on the diffuse large B-cell lymphoma page and in the treatment layer of this family. ([Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Rituximab](https://onco.cc/drugs/rituximab/), [CNS prophylaxis in aggressive B-cell lymphoma, and the evidence against it](https://onco.cc/terms/lymphoma-tx-cns-prophylaxis/), [The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest](https://onco.cc/terms/lymphoma-tx-regimen-alphabet/), [R-CHOP (lymphoma chemoimmunotherapy)](https://onco.cc/terms/r-chop/))

## Open problems

- No randomised trial has ever been run in this entity. The intensified regimens used for it were adopted from retrospective comparisons, and whether they are better than standard immunochemotherapy for an individual patient is not known.
- The test used to make the diagnosis identifies a narrower group than the biology does: the double-hit gene expression signature marks about twice as many patients as the rearrangements do, and those extra patients have the same outcome and are treated as ordinary diffuse large B-cell lymphoma.
- The two 2022 classifications handle MYC with BCL6 differently, so the same biopsy can yield two different diagnoses and two different trial eligibilities.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Diffuse_large_B-cell_lymphoma
- WHO Classification of Haematolymphoid Tumours, 5th edition: lymphoid neoplasms (Alaggio, Leukemia 2022): https://doi.org/10.1038/s41375-022-01620-2
- International Consensus Classification of Mature Lymphoid Neoplasms (Campo, Blood 2022): https://doi.org/10.1182/blood.2022015851
- Double-hit gene expression signature defines a distinct subgroup of germinal centre B-cell-like diffuse large B-cell lymphoma (Ennishi and Rosenwald, J Clin Oncol 2019): https://doi.org/10.1200/JCO.18.01583
- NCI PDQ: adult non-Hodgkin lymphoma treatment (health professional version): https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq

## Connected records

- cancers: [Burkitt lymphoma](https://onco.cc/cancers/burkitt-lymphoma/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Primary mediastinal (thymic) large B-cell lymphoma](https://onco.cc/cancers/primary-mediastinal-b-cell-lymphoma/)
- technologies: [FDG PET](https://onco.cc/technologies/fdg-pet/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- pathways: [MYC](https://onco.cc/pathways/myc/)
- targets: [BCL-2](https://onco.cc/targets/bcl2/)
- terms: [CNS prophylaxis in aggressive B-cell lymphoma, and the evidence against it](https://onco.cc/terms/lymphoma-tx-cns-prophylaxis/), [Double-hit / high-grade B-cell lymphoma](https://onco.cc/terms/double-hit-lymphoma/), [Indolent and aggressive lymphoma](https://onco.cc/terms/lymphoma-indolent-versus-aggressive/), [International Prognostic Index (IPI)](https://onco.cc/terms/ipi-score/), [R-CHOP (lymphoma chemoimmunotherapy)](https://onco.cc/terms/r-chop/), [The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest](https://onco.cc/terms/lymphoma-tx-regimen-alphabet/), [The two lymphoma classifications of 2022 (WHO-HAEM5 and ICC)](https://onco.cc/terms/lymphoma-classification-2022/)
- drugs: [Rituximab](https://onco.cc/drugs/rituximab/)

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JSON: https://onco.cc/api/v1/entities/high-grade-b-cell-lymphoma-myc-bcl2.json