Case Study: Bcl-6 and Its Relationship to Diffuse Large B-Cell Lymphoma

The following case study focuses on bcl-6 and its relationship to diffuse large B-cell lymphoma (DLBCL). Test your knowledge by reading the question below and making the proper selection.

All of the following are true regarding bcl-6 and its relationship to DLBCL except (select one):

  1. Bcl-6 is the most commonly involved oncogene in DLBCL.
  2. Bcl-6 positivity is associated with a favorable prognosis in DLBCL.
  3. Approximately one-quarter of DLBCLs are bcl-6 negative.
  4. Bcl-6 positive DLBCL seems to derive a therapeutic benefit from the addition of Rituxan to CHOP chemotherapy not seen in bcl-6 negative DLBCL.
  5. Bcl-6 expression is closely linked to the germinal-center phenotype as characterized by gene expression profiling.

Answer

  1. Bcl-6 positive DLBCL seems to derive a therapeutic benefit from the addition of Rituxan to CHOP chemotherapy not seen in bcl-6 negative DLBCL.

Explanation

Gene expression profiling has identified at least three clinically relevant phenotypes of DLBCL, which include germinal-center type, activated B-cell type, and mediastinal large B-cell lymphoma1. bcl-6, a marker of germinal center derivation, has been identified as a characteristic protein expressed in many, but not all, germinal-center type DLBCLs. It is the most commonly involved oncogene in DLBCL and confers a more favorable prognosis in DLBCL treated with conventional anthracycline-based chemotherapy2,3. Recently, an ECOG/SWOG Intergroup trial comparing CHOP to CHOP-R looked prospectively at bcl-6 expression in DLBCL. Prospective data showed that treatment with Rituximab in addition to standard CHOP chemotherapy improved survival in patients with bcl-6 negative disease but not with bcl-6 positive disease making overall outcomes similar in both populations4. Further correlative studies will help clarify prognostic indicators in the context of new therapeutic regimens. At the current time, gene expression profiling is not routinely done in the clinic but rather as an adjunct to clinical trials.

References

  1. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503-11.
  2. Hans CP, Weisenburger DD, Greiner TC, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275-82.
  3. Rosenwald A, Wright G, Chan WC, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(25):1937-47.
  4. Winter JN, Weller EA, Horning SJ, et al. Prognostic significance of BCL-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study. Blood. 2006;107(11):4207-13.

Additional Resource

Armitage J. How I treat patients with diffuse large B-cell lymphoma. Blood. 2007;110(1):29-36.

Case study submitted by Lanie Kasdan Francis, MD, of the University of Pittsburgh Medical Center and Christine Chen, MD, of Princess Margaret Hospital in Toronto.

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