Abstract
Human malignancies displaying a mature B cell phenotype include non-Hodgkin lymphoma, (NHL), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM). Analogous to most cancer types, the pathogenesis of these malignancies represents a multistep process involving the progressive and clonal accumulation of multiple genetic lesions affecting proto-oncogenes and tumor suppressor genes. However, several important features distinguish the mechanism and type of genetic alterations associated with NHL, CLL, and MM (Table 1).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Albagli O, Dhordain P., Deweindt C. et al. (1995) The BTB/POZ domain: a new protein-protein interaction motif common to DNA- and actin-binding proteins. Cell Growth & Differ. 6:1193– 1198
Allman D, Jain A, Dent A et al. (1996) BCL-6 expression during B-cell activation. Blood 87:5257– 5268.
Baron BW, Nucifora G, McCabe N et al. (1993) Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(q27;ql 1) in B-cell lymphomas. Proc. Natl. Acad. Sci. U.S.A. 90: 5262 – 5266.
Cattoretti G, Chang CC, Cechova K, et al. (1995) BCL-6 protein is expressed in germinal-center B cells. Blood 86: 45 – 53
Chang CC., Ye BH, Chaganti RSK et al. (1996) BCL-6, a POZ/zinc-finger protein, is a sequence- specific transcriptional repressor. Proc. Natl. Acad. Sci. U.S.A. 93: 6947 – 6952
Chen W, Iida S, Louie DC et al. (1998) Heterologous promoters fused to BCL-6 by chromosomal translocations affecting band 3q27 cause its deregulated expression during B-cell differentiation. Blood 91: 603 – 607
Dent AL, Shaffer AL, Yu X et al. (1997) Control of inflammation, cytokine expression, and germinal center formation by BCL-6. Science 276: 589 – 592
Deweindt C, Albagli O, Bernardin F et al. (1995) The LAZ3/BCL6 oncogene encodes a sequence- specific transcriptional inhibitor: a novel function for the BTB/POZ domain as an autonomous repressing domain. Cell Growth & Differ. 6: 1495 – 503
Gaidano G, Dalla-Favera R (1997) Molecular biology of Lymphomas. In: Principles and Practice of Oncology, DeVita, VT, Hellman, S., Rosenberg SA (eds) JB Lippincott Co (publ) p. 2131 – 2145
Gamberi B, Gaidano G, Parsa N et al. (1997) Microsatellite instability is rare in B-cell Non- Hodgkin’s Lymphoma. Blood 89: 975 – 979.
Johansson B, Mertens F, Mitelman F (1996) Primary vs. secondary neoplasia associated chromo-somal abnormalities - balanced rearrangements vs. genomic imbalances? Genes Chrom. & Cancer 16: 155 – 163.
Kerckaert JP, Deweindt C, Tilly H et al. (1993) LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas. Nature Genetics 5: 66 – 70.
Lo, Coco F, Ye BH, Lista F et al. (1994) Rearrangements of the BCL6 gene in diffuse large cell non-Hodgkin’s lymphoma. Blood 83: 1757 – 1759.
Migliazza A, Martinotti S, Chen S et al. (1995) Frequent somatic hypermutation of the 5’ noncoding region of the BCL6 gene in B-cell lymphoma. Proc. Natl. Acad. Sci. U.S.A. 92: 12520 – 12524.
Miki T, Kawamata N, Hirosawa S and Aoki N (1994) Gene involved in the 3q27 translocation associated with B-cell lymphoma, BCL5, encodes a Kruppel-like zinc-finger protein. Blood 83: 26 – 32.
Niu H, Ye BH, Dalla-Favera R (1998) Antigen-receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor. Genes & Development 12: 1953 – 1961.
Pasqualucci L, Migliazza A, Fracchiolla N et al. (1998) BCL-6 mutations in normal germinal center B cells: Evidence of somatic hypermutation acting outside Ig loci. Proc. Nat. Acad. Sci. USA 95: 11816 – 11821.
Seyfert VL, Allman D, He Y, and Staudt LM (1996) Transcriptional repression by the proto- oncogene BCL-6. Oncogene 12: 2331 – 2342.
Shen HM., Peters A, Baron B et al. (1998) Mutation of BCL-6 gene in normal B cells by the process of somatic hypermutation of Ig genes. Science 280: 1750 – 1752.
Ye BH, Cattoretti G, Shen Q et al. (1997) The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation. Nature Genetics 16: 161 – 170.
Ye BH, Chaganti S, Chang CC et al. (1995) Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma. EMBO J. 14: 6209 – 6217.
Ye BH, Lista F, Lo Coco F et al. (1993) Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma. Science 262: 747 – 750.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Dalla-Favera, R. et al. (1999). Molecular Pathogenesis of B Cell Malignancy: the Role of BCL-6. In: Melchers, F., Potter, M. (eds) Mechanisms of B Cell Neoplasia 1998. Current Topics in Microbiology and Immunology, vol 246. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60162-0_32
Download citation
DOI: https://doi.org/10.1007/978-3-642-60162-0_32
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-64283-8
Online ISBN: 978-3-642-60162-0
eBook Packages: Springer Book Archive