Expression of the Human Germinal Center-Associated Lymphoma (HGAL) Protein, A New Marker of Germinal Center B Cell Derivation

Yasodha Natkunam, Izidore S. Lossos, Behnaz Taidi, Shuchun Zhao, XiaoQing Lu, Feying Ding, Anne Sofie Hammer, Teresa Marafioti, Gerald E. Byrne Jr, Shoshana Levy, Roger A. Warnke, Ronald Levy

Blood First Edition Paper, prepublished online January 27, 2005; DOI 10.1182/blood-2004-08-3112.

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    Expression of the human germinal center-associated lymphoma (HGAL) protein, A new marker of germinal center B cell derivation
  • Abstract:

    We identified the Human Germinal center-Associated Lymphoma (HGAL) gene in gene expression profiling studies of diffuse large B-cell lymphoma (DLBCL). The expression of the HGAL gene correlated with survival in patients with DLBCL. The HGAL gene is the human homologue of M17, a mouse gene expressed specifically in normal germinal center B cells. Here we generated a monoclonal antibody against the HGAL protein and show that HGAL is expressed in the cytoplasm of GC-lymphocytes and in lymphomas of GC derivation. Among 718 lymphomas tested by immunohistochemistry on tissue microarrays, HGAL staining was found in follicular (103/107), Burkitt (40/40), mediastinal large B (7/8), and in DLBCL (103/151). Nodal and extranodal marginal zone lymphomas lacked HGAL staining. Lymphocyte predominant Hodgkin (12/17) and, surprisingly, classical Hodgkin (78/107) lymphomas were found to be positive. Hierarchical clustering of comparative immunohistologic results in DLBCL demonstrates that the expression of HGAL is similar to two other GC-associated proteins BCL6 and CD10, but different from two markers associated with a non-GC phenotype, MUM1/IRF4 and BCL2. The restricted expression and GC-specificity of HGAL protein suggest that it may have an important role in the diagnosis of specific lymphomas, and, potentially in the identification of subtypes associated with different prognoses.

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