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

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In contrast to most other B cell malignancies, which typically show reciprocal balanced chromosome translocations, no specific genetic alteration has yet been associated with this disease (Döhner et al. 1999). The low proliferative rate of B-CLL cells and their prolonged life span suggests that a critical alteration might be a defect in apoptosis (Caligaris-Cappio and Hamblin 1999). B-CLL has been the focus of intense investigations over many decades, and many studies revealed a number of surprising and unexpected findings in the light of previously obtained knowledge on healthy and transformed B lymphocytes.

43 References . . . . . . . . . . . . . . . . . . . . . . . . . 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.

1999), although some exceptions have been reported (Döhner et al. 1999; Buhmann et al. 2002). Instead, the major genomic alterations are deletions and amplifications. This observation, together with the marginal zone B cell-like phenotype (see Sect. 4, above), suggests that B-CLL may lack chromosome translocations because the mechanisms involved in these aberrations, somatic hypermutation and Ig class switch, are no longer active in these cells (Fig. 2). As to what may be the transforming mechanisms leading to B-CLL development, this is an open question and out of the scope of this review.

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