MYC translocation partner gene determines survival of patients with large B‐cell lymphoma with MYC ‐ or double‐hit MYC / BCL 2 translocations

In large B‐cell lymphoma ( LBCL ) MYC ‐ and MYC / BCL 2 double‐hit ( DH ) translocations have been associated with inferior survival. We hypothesised that the negative prognostic impact of MYC translocation was determined by an immunoglobulin MYC translocation partner gene ( IG ‐ MYC ), as opposed to a non‐immunoglobulin partner gene (non IG ‐ MYC ). In a prospective, unselected cohort of 237 LBCL patients MYC and BCL 2 translocations were identified by Flourescent in situ hybridisation ( FISH ) with split probes. MYC translocation partner gene was identified by IGH / MYC fusion probes and/or kappa/lambda split probes. Clinical data were collected from patient files. MYC translocation was identified in 28/225 patients. IG ‐ MYC translocation partner gene was identified in 12/24 patients. DH translocation was identified in 23/228 patients. IG ‐ MYC translocation partner gene was identified in 9/19 DH patients. Neither MYC ‐nor DH translocation showed correlation with survival. However, MYC translocation with IG ‐ MYC translocation partner gene was associated with worse OS compared with both MYC translocation with non IG ‐ MYC translocation partner gene ( P = 0.02) as well as absence of MYC translocation ( P = 0.03). In patients with DH a similar, however, stronger correlation was seen ( P = 0.003 and P = 0.0004 respectively). MYC – or DH translocation with non IG ‐ MYC translocation partner gene was not associated with worse overall survival ( P = 0.2 and P = 0.3 respectively). Most patients received Rituximab (86%) and CHOP / CHOP ‐like chemotherapy regimes (81%). We suggest that prognostic stratification of LBCL patients by MYC and/or DH translocations should include identification of MYC translocation partner gene because approximately half of the cases harbour non IG ‐ MYC translocation partner genes with no or minor influence on survival.