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New Insights into the Phenotype and Cell Derivation of B Cell Chronic Lymphocytic Leukemia

  • Chapter
Chronic Lymphocytic Leukemia

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 294))

Abstract

For many decades, B cell chronic lymphocytic leukemia (B-CLL) stood out as a B cell-derived malignancy that was difficult to position within the framework of the available B cell differentiation scheme: First, the histology as well as the immunophenotype did not quite resemble that of any normal lymphocyte; second, in contrast to almost all other B cell tumor subtypes, the immunoglobulin variable region (IgV) genes of B-CLL cases could be either unmutated or somatically mutated; third, the genomic lesions observed in B-CLL were markedly distinct from those of the other major B cell malignancies, which typically exhibit balanced chromosome translocations. Recent advances in the characterization of both B-CLL and normal B cell subpopulations by phenotypic analysis, global gene expression profiling, as well as extensive IgV gene repertoire analyses have shed new light on the phenotype and the cell derivation of B-CLL and provided novel hypotheses concerning its pathogenesis. Here we summarize recent work relevant to these issues and conclude that B-CLLmay be derived from a cell that can be referred to as a marginal zone B cell. Moreover, we propose that the lack of chromosomal translocations in B-CLL may be related to their derivation frommarginal zone B cells, since somatic hypermutation and Ig class switch, the processes that generate chromosome translocations in most germinal center (GC)-derived malignancies, are no longer active in marginal zone B cells. Also, we discuss similarities and differences between B-CLL and hairy cell leukemia (HCL) and suggest that alsoHCL may be derived froma post-GC memory or marginal zone B cell.

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  1. Institute for Cancer Genetics, Columbia University, 1150 St. Nicholas Ave., New York, NY, 10032, USA

    R. Dalla-Favera

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Klein, U., Dalla-Favera, R. (2005). New Insights into the Phenotype and Cell Derivation of B Cell Chronic Lymphocytic Leukemia. In: Chronic Lymphocytic Leukemia. Current Topics in Microbiology and Immunology, vol 294. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-29933-5_3

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