MYC translocation and/or BCL 2 protein expression are associated with poor prognosis in diffuse large B-cell lymphoma

Cancer Sci. 2016 Jun;107(6):853-61. doi: 10.1111/cas.12942. Epub 2016 May 6.

Abstract

Genomic alterations and protein expression levels have been established as prognostic factors for survival in patients with diffuse large B-cell lymphoma (DLBCL). In particular, double-hit DLBCL (DHL), which exhibits translocations in MYC and BCL2 and/or BCL6, is known to be associated with a poor prognosis. However, the clinical significance of gene alterations and protein expression levels for MYC, B-cell lymphoma (BCL)2, and BCL6 are unclear. In this study, we analyzed 61 adult patients diagnosed with DLBCL without DHL, who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone, or similar regimens. There were no differences in the distribution of MYC expression rates among the different MYC gene statuses. In log-rank tests, MYC translocation was a prognostic factor for overall survival (OS; P = 0.011), whereas BCL2 and BCL6 translocation were not prognostic indicators (P = 0.999 and P = 0.925, respectively). Although the expression levels of MYC and BCL6 were not significantly associated with OS, the expression of BCL2 was a prognostic factor for OS (P = 0.027). Furthermore, copy number gains in the MYC, BCL2, and BCL6 genes did not affect OS. MYC translocation (hazard ratio, 4.769; range, 1.518-14.98; P = 0.007) and BCL2 protein expression (hazard ratio, 3.072; range, 1.002-9.413; P = 0.049) were independent prognostic factors for survival in multivariate analyses. In conclusion, MYC translocation and BCL2 expression may need to be investigated at the initial diagnosis to predict prognosis in patients with DLBCL.

Keywords: BCL2; BCL6; MYC; diffuse large B-cell lymphoma; prognostic factor.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Female
  • Genes, myc*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / diagnosis*
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Male
  • Middle Aged
  • Prednisolone / therapeutic use
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Rituximab / therapeutic use
  • Translocation, Genetic / genetics*
  • Vincristine / therapeutic use
  • Young Adult

Substances

  • BCL2 protein, human
  • BCL6 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisolone