# Double-hit / high-grade B-cell lymphoma

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

## TL;DR

Double-hit lymphoma is a large B-cell lymphoma with rearrangements of two oncogenes (MYC plus BCL2 and/or BCL6), which behaves aggressively and often escapes R-CHOP.

## Summary

Double-hit lymphoma is a large B-cell lymphoma carrying rearrangements of two oncogenes, MYC together with BCL2 and/or BCL6, which behaves aggressively and often escapes R-CHOP. The WHO 2022 classification names the MYC and BCL2 form high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBL-DH-BCL2), while the MYC and BCL6 double hit has been reclassified as DLBCL not otherwise specified. It accounts for a small minority of DLBCL and is often treated with the more intensive DA-EPOCH-R regimen rather than R-CHOP. CAR-T outcomes in ZUMA-7 were similar to those in other large B-cell lymphomas, so the diagnosis does not exclude cellular therapy. Readers meet it on the DLBCL and HIV-associated lymphoma pages and through the BCL-2 target.

## Fields

- Kind: Term
- Last checked: 2026-09-07

## Notes

- The rates, and the difference between rearrangement and expression. In 442 unselected diffuse large B-cell lymphomas treated on the RICOVER study and read by both FISH and immunohistochemistry, MYC was rearranged in 8.8%, BCL2 in 13.5% and BCL6 in 28.7%, while MYC protein above the 40% threshold was present in 31.8%, BCL2 protein in 79.6% and BCL6 protein in 82.8% (Horn 2013). Protein co-expression is therefore several times commoner than rearrangement and is a different finding: in a 167-patient cohort, MYC protein was detected in 29% and BCL2 in 44% with both in 21%, against a MYC translocation in 11%, and MYC protein predicted worse survival only where BCL2 protein was present too (Johnson 2012). MYC was mapped to the translocated region of chromosome 8 in Burkitt lymphoma in 1982 and the partner is always an immunoglobulin locus (Dalla-Favera 1982); the WHO fifth edition makes high-grade B-cell lymphoma with MYC and BCL2 rearrangements an entity of its own (Alaggio 2022).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Diffuse_large_B-cell_lymphoma
- NCI Dictionary of Cancer Terms: double-hit lymphoma: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/double-hit-lymphoma
- 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
- Johnson et al., J Clin Oncol 2012: concurrent MYC and BCL2 protein expression in diffuse large B-cell lymphoma treated with R-CHOP: https://doi.org/10.1200/JCO.2011.41.0985
- 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
- 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

- cancers: [Burkitt lymphoma](https://onco.cc/cancers/burkitt-lymphoma/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma)](https://onco.cc/cancers/high-grade-b-cell-lymphoma-myc-bcl2/), [HIV-associated (AIDS-related) lymphomas](https://onco.cc/cancers/hiv-associated-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- 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/)
- terms: [CNS prophylaxis in aggressive B-cell lymphoma, and the evidence against it](https://onco.cc/terms/lymphoma-tx-cns-prophylaxis/)
- trials: [TRANSCEND NHL 001](https://onco.cc/trials/transcend-nhl-001/)
- key papers: [Dose-adjusted EPOCH-R compared with R-CHOP as frontline therapy for diffuse large B-cell lymphoma: clinical outcomes of the phase III intergroup trial Alliance/CALGB 50303](https://onco.cc/key-papers/paper-calgb-50303-da-epoch-r-vs-r-chop-jco-2019/), [Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study](https://onco.cc/key-papers/paper-transcend-nhl-001-liso-cel-lancet-2020/)
- 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/)

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