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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.
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.
In plain words · MYC (Myc proto-oncogene protein) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Skin cancer, Multiple myeloma and 5 more.
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.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
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.
“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.”
Horn et al., Blood 2013No approval uses this readout as a threshold. It is defined by Alaggio et al., Leukemia 2022: the fifth edition of the WHO classification of haematolymphoid tumours, lymphoid neoplasms.
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