Chronic Lymphocytic Leukemia (Current Topics in Microbiology by by Federico Caligaris-Cappio (Editor), Riccardo Dalla Favera

By by Federico Caligaris-Cappio (Editor), Riccardo Dalla Favera (Editor)

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Immunol Today 19:480–485 7. Ghia P, ten Boekel E, Sanz E, de la Hera A, Rolink A, Melchers F (1996) Ordering of human bone marrow B lymphocyte precursors by single-cell polymerase chain reaction analyses of the rearrangement status of the immunoglobulin H and L chain gene loci. J Exp Med 184:2217–2229 8. Grawunder U, Leu TM, Schatz DG, Werner A, Rolink AG, Melchers F, Winkler TH (1995) Down-regulation of RAG1 and RAG2 gene expression in preB cells after functional immunoglobulin heavy chain rearrangement.

44 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.

However, while these New Insights into the Phenotype and Cell Derivation of B Cell 37 analyses demonstrate a high level of concordance between IgV mutational status and ZAP-70 expression, the correlation is not absolute, suggesting that multiple determinants may be involved in the difference between the two subtypes of B-CLL. Several studies comparing IgV gene mutation levels with IgV gene usage in B-CLL led to the conclusion that the expression of certain IgV gene segments correlates with their mutational status, and therefore also with clinical prognosis (this topic has been extensively reviewed by Chiorazzi and Ferrarini 2003).

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