Rearrangement of the <i>BCL6</i> gene in B‐cell lymphoid neoplasms: comparison with lymphomas associated with <i>BCL2</i> rearrangement

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<jats:p>We report a series of B‐cell neoplasms with regard to rearrangement of the <jats:italic>BCL6</jats:italic> gene on chromosome band 3q27. Southern blot analysis using probes from the major translocation cluster (MTC) region of the <jats:italic>BCL6</jats:italic> revealed rearrangement in 21/197 patients (10.7%) with B‐cell neoplasms studied at presentation, and 11/25 patients (44%) first studied at relapse. In non‐Hodgkin's lymphoma (NHL) studied at diagnosis, rearrangements of the <jats:italic>BCL6</jats:italic> gene were not closely associated with a specific histopathologic subtype but distributed in subcategories in the Working Formulation. The incidence in follicular lymphoma was 12.1%, with significantly higher frequency in mixed and large cell subtypes, and that in diffuse aggressive lymphoma was 14.1%. Comigration analysis using probes from the immunoglobulin genes revealed association of the <jats:italic>BCL6</jats:italic> gene with one of the three immunoglobulin loci in 9/25 cases analysed. A comparative study between NHL associated either with <jats:italic>BCL2</jats:italic> or <jats:italic>BCL6</jats:italic> rearrangement showed that advanced disease and bone marrow involvement were more frequent in <jats:italic>BCL2</jats:italic>(+) NHL. In contrast, extranodal involvement was more frequently observed in the <jats:italic>BCL6</jats:italic>(+) NHL. The survival curve of <jats:italic>BCL6</jats:italic>(+) NHL was characterized by a rapid decline followed by a plateau. Of the total of 32 <jats:italic>BCL6</jats:italic>(+) patients, six carried both <jats:italic>BCL2</jats:italic> and <jats:italic>BCL6</jats:italic> rearrangements; five of these six showed clinicopathological properties characteristic of follicular lymphoma, suggesting that the presence of the two genetic abnormalities does not necessarily have synergistic effects on malignant phenotypes. The high level of <jats:italic>BCL6</jats:italic> expression in follicular lymphoma cell lines carrying a <jats:italic>BCL2</jats:italic> rearrangement suggests that the deregulated <jats:italic>BCL2</jats:italic> gene may have an effect on the development of genetic abnormalities of the <jats:italic>BCL6</jats:italic> gene. The present study suggests that <jats:italic>BCL6</jats:italic> gene rearrangement is primarily involved in large cell lymphoma irrespective of growth pattern of neoplastic cells, and that <jats:italic>BCL6</jats:italic>(+)<jats:italic>BCL2</jats:italic>(−) NHL could be curable with modern intensive chemotherapy.</jats:p>

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