BCL-6 Mutations Are Associated with Immunoglobulin Variable Heavy Chain Mutations in B-Cell Chronic Lymphocytic Leukemia

作者: Anna Migliazza , Luca Baldini , Antonino Neri , Riccardo Dalla-Favera , Laura Pasqualucci

DOI:

关键词: Germline mutationB cellCell of originPhenotypeSomatic hypermutationChronic lymphocytic leukemiaGeneticsGeneAntibodyBiology

摘要: The cell of origin B-cell chronic lymphocytic leukemia (B-CLL) is still uncertain. Recent studies have indicated that a fraction B-CLL displays somatically mutated immunoglobulin variable heavy chain (IgVH) genes, which suggests an from post-germinal center (GC) B cell. It has been shown the 5′ noncoding region BCL-6 proto-oncogene affected by mutations in normal GC B-lymphocytes and lymphoid malignancies displaying GC/post-GC phenotype. To further explore cellular B-CLL, we analyzed 34 cases for IgVH genes. We found genes 24 (73%) 33 samples (average frequency, 6.5 × 10−2/bp) 8 (24%) 0.14 10−2/bp cases). occurrence was restricted to those mutations. Analysis protein expression as marker phenotype showed that, regardless presence or mutations, B-CLLs express at levels clearly below transformed cells. These results indicate subset derives exposed somatic hypermutation mechanism support hypothesis result same process targets

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