Pedersen, Mette Ø4; Gang, Anne O3; Poulsen, Tim S3; Knudsen, Helle3; Lauritzen, Anne F3; Nielsen, Signe L5; Klausen, Tobias W3; Nørgaard, Peter3
1 Miljø- og Arbejdsmedicin, Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet2 Molecular Disease Biology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Miljø- og Arbejdsmedicin, Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet5 Molecular Disease Biology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, Københavns Universitet
In large B-cell lymphoma (LBCL) MYC- and MYC/BCL2 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 (nonIG-MYC). In a prospective, unselected cohort of 237 LBCL patients MYC and BCL2 translocations were identified by fluorescent 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 nonIG-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 nonIG-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 nonIG-MYC translocation partner genes with no or minor influence on survival.
European Journal of Haematology, 2014, Vol 92, Issue 1, p. 42-48