# Double-hit and triple-hit: MYC with BCL2 and BCL6 rearrangement

Source: https://onco.cc/biomarkers/double-hit-rearrangement/  
OnCo record `double-hit-rearrangement` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A lymphoma that carries a rearrangement of MYC, the gene that drives growth, together with one of BCL2 or BCL6, the genes that stop a cell dying. Having both is far worse than having either, and it usually means a stronger treatment than standard R-CHOP.

## Summary

MYC was mapped to the chromosome 8 region translocated to chromosome 2, 14 or 22 in Burkitt lymphoma cells in 1982, and the partner is always an immunoglobulin locus (Dalla-Favera 1982). In Burkitt lymphoma MYC is the defining lesion. In large B-cell lymphoma it is a minority event that matters mostly through what accompanies it: in 442 patients treated on the RICOVER study, MYC was rearranged in 8.8%, BCL2 in 13.5% and BCL6 in 28.7%, and MYC translocation predicted worse survival independently of the International Prognostic Index (Horn 2013).

A double hit is MYC plus BCL2; a triple hit adds BCL6. The two lesions are complementary: MYC drives proliferation and would ordinarily trigger apoptosis, and BCL2 removes that safeguard. The WHO fifth edition recognises high-grade B-cell lymphoma with MYC and BCL2 rearrangements as a separate entity rather than a variant of diffuse large B-cell lymphoma (Alaggio 2022).

The partner matters. A MYC rearrangement to an immunoglobulin partner carries a worse outlook than one to a non-immunoglobulin partner, which is an argument for a dual-fusion probe rather than a break-apart probe alone.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-30
- Also known as: Double hit lymphoma; Triple hit lymphoma; DHL; HGBL-DH; high-grade B-cell lymphoma with MYC and BCL2 rearrangements; MYC rearrangement FISH
- Tags: biomarker; lymphoma

## Sources

- Dalla-Favera et al., PNAS 1982: human c-myc lies in the chromosome 8 region translocated in Burkitt lymphoma: https://doi.org/10.1073/pnas.79.24.7824
- Horn et al., Blood 2013: MYC, BCL2 and BCL6 rearrangement and expression in 442 RICOVER patients: https://doi.org/10.1182/blood-2012-06-435842
- Alaggio et al., Leukemia 2022: the fifth edition of the WHO classification of haematolymphoid tumours, lymphoid neoplasms: https://doi.org/10.1038/s41375-022-01620-2

## Connected records

- biomarkers: [BCL2 rearrangement, t(14;18)](https://onco.cc/biomarkers/bcl2-rearrangement/), [Double expressor: MYC and BCL2 protein together by immunohistochemistry](https://onco.cc/biomarkers/myc-bcl2-double-expressor/)
- 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/), [Richter transformation of chronic lymphocytic leukaemia](https://onco.cc/cancers/richter-transformation-cll/)
- technologies: [Cytogenetics and FISH](https://onco.cc/technologies/cytogenetics-fish/)
- targets: [BCL-2](https://onco.cc/targets/bcl2/), [BCL6](https://onco.cc/targets/bcl6/), [MYC](https://onco.cc/targets/myc-gene/)
- pathways: [Intrinsic apoptosis (BCL-2 family)](https://onco.cc/pathways/apoptosis-bcl2/), [MYC](https://onco.cc/pathways/myc/), [The germinal centre reaction](https://onco.cc/pathways/germinal-centre-reaction/)
- terms: [CNS prophylaxis in aggressive B-cell lymphoma, and the evidence against it](https://onco.cc/terms/lymphoma-tx-cns-prophylaxis/), [Cytogenetics and karyotype](https://onco.cc/terms/cytogenetics/), [FISH / ISH (in situ hybridisation)](https://onco.cc/terms/fish/), [The germinal centre: why lymphoma starts where antibodies are made](https://onco.cc/terms/lymphoma-bio-germinal-centre/)

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