Point mutations of the BCL-6 gene

Clinical and prognostic correlation in B-diffuse large cell lymphoma

U. Vitolo, B. Botto, D. Vivenza, V. Zagonel, A. Gloghini, D. Novero, G. Parvis, R. Calvi, C. Ariatti, I. Milan, M. Bertini, C. Boccomini, R. Freilone, P. Pregno, L. Orsucci, G. Palestro, G. Saglio, A. Carbone, E. Gallo, G. Gaidano

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Although point mutations of the 5′ noncoding regions of the BCL-6 proto-oncogene are frequently detected in B-diffuse large cell lymphoma (B-DLCL), a thorough analysis of the clinical correlation of these mutations has not been performed to date. In this study, BCL-6 mutations were examined by DNA direct sequencing in 103 patients with B-DLCL. BCL-6 mutations were found in 53/103 patients, including 38/76 treated with standard chemotherapy and 15/27 treated with autologous stem cell transplantation (ASCT) up front. The presence of BCL-6 mutations was correlated with clinical features. at diagnosis and outcome. Mutated patients had a significantly higher LDH level (66% vs 38%, P <0.05), and bulky disease (51% vs 32%, P = 0.05). In the whole series of patients BCL-6 mutations did not affect CR and OS. Patients with BCL-6 mutations tended to have a prolonged 5-years DFS and FFS compared to those without mutations (DFS 82% vs 63%, FFS 63% vs 49%). Among B-DLCL treated with standard chemotherapy, mutated patients showed a significantly improved 5-year DFS (85% vs 61%, P <0.05) and, notably, the only four relapses observed among mutated patients occurred in less than 8 months. The multivariate regression analysis (P <0.01) with DFS as endpoint confirmed the independent prognostic value of BCL-6 mutations. There was a trend for 5-year failure-free survival to be better for patients with BCL-6 mutations (63% vs 43%, P = 0.09). In the 27 patients treated with ASCT, BCL-6 mutations did not correlate with outcome. These results suggest that BCL-6 mutations may predict a higher chance of being free of disease in B-DLCL treated with standard chemotherapy. Larger series of patients need to be analyzed to evaluate the clinical relevance of BCL-6 mutations properly.

Original languageEnglish
Pages (from-to)268-275
Number of pages8
JournalLeukemia
Volume16
Issue number2
DOIs
Publication statusPublished - 2002

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Lymphoma, Large B-Cell, Diffuse
Point Mutation
Mutation
Genes
Stem Cell Transplantation
Drug Therapy
Proto-Oncogenes
DNA Sequence Analysis
Multivariate Analysis
Regression Analysis

Keywords

  • B-DLCL
  • BCL-6 mutations
  • BCL-6 rearrangement
  • Standard chemotherapy

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Point mutations of the BCL-6 gene : Clinical and prognostic correlation in B-diffuse large cell lymphoma. / Vitolo, U.; Botto, B.; Vivenza, D.; Zagonel, V.; Gloghini, A.; Novero, D.; Parvis, G.; Calvi, R.; Ariatti, C.; Milan, I.; Bertini, M.; Boccomini, C.; Freilone, R.; Pregno, P.; Orsucci, L.; Palestro, G.; Saglio, G.; Carbone, A.; Gallo, E.; Gaidano, G.

In: Leukemia, Vol. 16, No. 2, 2002, p. 268-275.

Research output: Contribution to journalArticle

Vitolo, U, Botto, B, Vivenza, D, Zagonel, V, Gloghini, A, Novero, D, Parvis, G, Calvi, R, Ariatti, C, Milan, I, Bertini, M, Boccomini, C, Freilone, R, Pregno, P, Orsucci, L, Palestro, G, Saglio, G, Carbone, A, Gallo, E & Gaidano, G 2002, 'Point mutations of the BCL-6 gene: Clinical and prognostic correlation in B-diffuse large cell lymphoma', Leukemia, vol. 16, no. 2, pp. 268-275. https://doi.org/10.1038/sj/leu/2402349
Vitolo, U. ; Botto, B. ; Vivenza, D. ; Zagonel, V. ; Gloghini, A. ; Novero, D. ; Parvis, G. ; Calvi, R. ; Ariatti, C. ; Milan, I. ; Bertini, M. ; Boccomini, C. ; Freilone, R. ; Pregno, P. ; Orsucci, L. ; Palestro, G. ; Saglio, G. ; Carbone, A. ; Gallo, E. ; Gaidano, G. / Point mutations of the BCL-6 gene : Clinical and prognostic correlation in B-diffuse large cell lymphoma. In: Leukemia. 2002 ; Vol. 16, No. 2. pp. 268-275.
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AU - Vitolo, U.

AU - Botto, B.

AU - Vivenza, D.

AU - Zagonel, V.

AU - Gloghini, A.

AU - Novero, D.

AU - Parvis, G.

AU - Calvi, R.

AU - Ariatti, C.

AU - Milan, I.

AU - Bertini, M.

AU - Boccomini, C.

AU - Freilone, R.

AU - Pregno, P.

AU - Orsucci, L.

AU - Palestro, G.

AU - Saglio, G.

AU - Carbone, A.

AU - Gallo, E.

AU - Gaidano, G.

PY - 2002

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