{"entity":{"id":"double-hit-lymphoma","kind":"term","name":"Double-hit / high-grade B-cell lymphoma","aka":[],"tldr":"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.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Diffuse_large_B-cell_lymphoma","links":[{"label":"NCI Dictionary of Cancer Terms: double-hit lymphoma","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/double-hit-lymphoma"},{"label":"Horn et al., Blood 2013: MYC, BCL2 and BCL6 rearrangement and expression in 442 RICOVER patients","url":"https://doi.org/10.1182/blood-2012-06-435842"},{"label":"Johnson et al., J Clin Oncol 2012: concurrent MYC and BCL2 protein expression in diffuse large B-cell lymphoma treated with R-CHOP","url":"https://doi.org/10.1200/JCO.2011.41.0985"},{"label":"Dalla-Favera et al., PNAS 1982: human c-myc lies in the chromosome 8 region translocated in Burkitt lymphoma","url":"https://doi.org/10.1073/pnas.79.24.7824"},{"label":"Alaggio et al., Leukemia 2022: the fifth edition of the WHO classification of haematolymphoid tumours, lymphoid neoplasms","url":"https://doi.org/10.1038/s41375-022-01620-2"}],"tags":[],"related":[],"cancers":["dlbcl","burkitt-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":["bcl2","myc-gene","bcl6"],"drugs":[],"companies":[],"institutions":[],"pathways":["myc","apoptosis-bcl2"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"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)."],"category":"Biomarkers"},"route":"/terms/double-hit-lymphoma/","neighbours":{"cancer":[{"id":"burkitt-lymphoma","kind":"cancer","name":"Burkitt lymphoma","route":"/cancers/burkitt-lymphoma/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"high-grade-b-cell-lymphoma-myc-bcl2","kind":"cancer","name":"High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma)","route":"/cancers/high-grade-b-cell-lymphoma-myc-bcl2/"},{"id":"hiv-associated-lymphoma","kind":"cancer","name":"HIV-associated (AIDS-related) lymphomas","route":"/cancers/hiv-associated-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}],"target":[{"id":"bcl2","kind":"target","name":"BCL-2","route":"/targets/bcl2/"},{"id":"bcl6","kind":"target","name":"BCL6","route":"/targets/bcl6/"},{"id":"myc-gene","kind":"target","name":"MYC","route":"/targets/myc-gene/"}],"pathway":[{"id":"apoptosis-bcl2","kind":"pathway","name":"Intrinsic apoptosis (BCL-2 family)","route":"/pathways/apoptosis-bcl2/"},{"id":"myc","kind":"pathway","name":"MYC","route":"/pathways/myc/"}],"term":[{"id":"lymphoma-tx-cns-prophylaxis","kind":"term","name":"CNS prophylaxis in aggressive B-cell lymphoma, and the evidence against it","route":"/terms/lymphoma-tx-cns-prophylaxis/"}],"trial":[{"id":"transcend-nhl-001","kind":"trial","name":"TRANSCEND NHL 001","route":"/trials/transcend-nhl-001/"}],"paper":[{"id":"paper-calgb-50303-da-epoch-r-vs-r-chop-jco-2019","kind":"paper","name":"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","route":"/key-papers/paper-calgb-50303-da-epoch-r-vs-r-chop-jco-2019/"},{"id":"paper-transcend-nhl-001-liso-cel-lancet-2020","kind":"paper","name":"Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study","route":"/key-papers/paper-transcend-nhl-001-liso-cel-lancet-2020/"}],"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/lymphoma-roadmap/"}]}}