Recent prognostic factors in diffuse large B-cell lymphoma indicate NF-κB pathway as a target for new therapeutic strategies

Alessandro Pavan, Michele Spina, Vincenzo Canzonieri, Silvia Sansonno, Giuseppe Toffoli, Valli De Re

Research output: Contribution to journalArticle

Abstract

The diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoid cancer. The classical chemotherapy regimen given to these patients was the CHOP (Cyclophosphamide, Hydroxydaunorubicin or Adriamycin, Oncovin or Vincristine, Prednisone or Prednisolone), but recently rituximab with CHOP (R-CHOP) increased the number of cases responding to first line therapy. DLBCL classification identified three principle subgroups. The first one, named germinal centre B cell-like (GCB), responds to both CHOP and R-CHOP treatment and it is mainly characterised by the expression of markers like Bcl-6 and CD10. The second, the activated B-cell like (ABC), has a worse prognosis in comparison with GCB, and is mainly characterised by the expression of IRF-4, PRDM1 and NF-κB. It is interesting to notice that IRF-4 and PRDM1 are under the transcriptional control of NF-κB, whose high activation level is associated with a worse prognosis. The third one, mediastinal large B-cell lymphoma (PMBCL) is an uncommon subtype characteristically found in young females. Gene expression profiling suggests that this disease resembles Hodgkin lymphoma more than other types of DLBCL. The impact of rituximab on the outcome of patients with PMBCL has still not been fully assessed. It was seen that rituximab inhibits NF-κB pathway in vitro. However, the clinical significance of this finding is still unknown, because both ABC and GCB DLBCL show a significant improvement of overall survival after R-CHOP treatment. In this review, the NF-κB pathway is suggested as a target for new chemotherapy strategies based on the association of CHOP with molecules more effective than rituximab in this pathway inhibition.

Original languageEnglish
Pages (from-to)2048-2058
Number of pages11
JournalLeukemia and Lymphoma
Volume49
Issue number11
DOIs
Publication statusPublished - 2008

Keywords

  • Chemotherapeutic approaches
  • CHOP
  • DLBCL
  • Drug resistance
  • Hodgkin disease
  • Lymphoma
  • Molecular genetics
  • Neoplasia
  • NF-κB
  • Pharmacotherapeutics
  • R-CHOP

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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