{"entity":{"id":"double-hit-rearrangement","kind":"biomarker","name":"Double-hit and triple-hit: MYC with BCL2 and BCL6 rearrangement","aka":["Double hit lymphoma","Triple hit lymphoma","DHL","HGBL-DH","high-grade B-cell lymphoma with MYC and BCL2 rearrangements","MYC rearrangement FISH"],"tldr":"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).\n\nA 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).\n\nThe 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.","asOf":"2026-09-30","links":[{"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":"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":"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":["biomarker","lymphoma"],"related":["bcl2-rearrangement","myc-bcl2-double-expressor"],"cancers":["dlbcl","burkitt-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":["cytogenetics-fish"],"targets":["myc-gene","bcl2","bcl6"],"drugs":[],"companies":[],"institutions":[],"pathways":["myc","apoptosis-bcl2","germinal-centre-reaction"],"terms":["fish","cytogenetics","lymphoma-tx-cns-prophylaxis","lymphoma-bio-germinal-centre"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"myc-gene","measurement":"fish-ratio","scoringRule":{"text":"Interphase fluorescence in situ hybridisation for MYC, BCL2 and BCL6, reported as rearranged or not for each. Double hit means MYC plus BCL2 rearrangement, triple hit means MYC plus BCL2 plus BCL6. Most laboratories screen on MYC protein expression and run the full panel where it exceeds the local threshold, which will miss a minority of rearranged cases with low protein.","quote":"MYC rearrangements occur in 5% to 10% of diffuse large B-cell lymphomas (DLBCL) and confer an increased risk to cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (CHOP) and rituximab (R)-CHOP treated patients.","source":"https://doi.org/10.1182/blood-2012-06-435842","sourceLabel":"Horn et al., Blood 2013"},"thresholds":[],"definedBy":{"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"},"tests":[],"assays":[],"companionDiagnostics":[],"forPatient":"This result usually changes the plan. A double-hit lymphoma is generally treated with a more intensive regimen than R-CHOP and with treatment aimed at protecting the brain and spinal cord, because this type reaches them more often. The evidence for the stronger regimen comes from comparisons between groups of patients rather than from a randomised trial, which is worth knowing when weighing the extra side effects."},"route":"/biomarkers/double-hit-rearrangement/","neighbours":{"biomarker":[{"id":"bcl2-rearrangement","kind":"biomarker","name":"BCL2 rearrangement, t(14;18)","route":"/biomarkers/bcl2-rearrangement/"},{"id":"myc-bcl2-double-expressor","kind":"biomarker","name":"Double expressor: MYC and BCL2 protein together by immunohistochemistry","route":"/biomarkers/myc-bcl2-double-expressor/"}],"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":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"richter-transformation-cll","kind":"cancer","name":"Richter transformation of chronic lymphocytic leukaemia","route":"/cancers/richter-transformation-cll/"}],"technology":[{"id":"cytogenetics-fish","kind":"technology","name":"Cytogenetics and FISH","route":"/technologies/cytogenetics-fish/"}],"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/"},{"id":"germinal-centre-reaction","kind":"pathway","name":"The germinal centre reaction","route":"/pathways/germinal-centre-reaction/"}],"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/"},{"id":"cytogenetics","kind":"term","name":"Cytogenetics and karyotype","route":"/terms/cytogenetics/"},{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"id":"lymphoma-bio-germinal-centre","kind":"term","name":"The germinal centre: why lymphoma starts where antibodies are made","route":"/terms/lymphoma-bio-germinal-centre/"}]}}