Factors Responsible for Bcell Clonal Expansion

4.1.1. Genetic alterations

Chromosomal translocations are the most common genetic alterations associated with B-cell lymphomagenesis. These changes are responsible for the functional alteration of a variety of genes contributing to B-cell transformation, including proto-oncogenes and genes encoding the proteins involved in the control of the cell cycle, differentiation and programmed cell death. Of interest is the fact that at least one specific chromosomal abnormality characterizes each lymphoma subtype. These findings support the hypothesis that distinct molecular pathways underlie the pathogenesis of different B lymphoma histotypes, thus providing the biological bases for the broad clinicopathological heterogeneity displayed by these lymphoproliferative disorders [30],

Several chromosomal abnormalities have been described in patients with SS having an associated lymphoma (Table 2). The first one is the t(14;18) chromosomal traslocation, which is the cytogenetic hallmark of follicle center lymphoma (FCL) [31]. This translo cation results in the deregulated expression of the bcl-2 gene: the translocation juxtaposes the bcl-2 gene with Ig heavy chain locus leading to an inappropriately high synthesis of bcl-2 protein [32], Although the function of the bcl-2 gene product is not yet clear, the presence of high levels of bcl-2 protein inhibits B-cell apopto-sis thus increasing B-cell survival and this may lead to an increased chance of neoplastic transformation. Some authors have studied the presence of this traslocation in SS patients with lymphoma. Fox et al. [33], using both Southern blot and the polimerase chain reaction (PCR), demonstrated that 50% of SS-associated lymphomas present this translocation which was not detected in SS patients without lymphoma, or in those with pseudolymphoma. Translocations of this bcl-2 gene were also observed by Pisa et al. [34] in 5 of 7 SS-associated lymphomas by Southern blot analysis, and no bcl-2 translocations were detected in 50 consecutive salivary gland biopsies of patients with SS lacking clinical evidence of coexistent lymphoma or in the pre-lymphoma biopsies from the same patient. Other authors failed to identify this t(14;18) translocation in any of the lip biopsies showing heavy chain monoclonality or in any of the extrasalivary gland lymphomas [35], We may conclude that analysis of bcl-2 translocations in tissue biopsies will aid in the diagnosis of lymphoma, although a negative result would not eliminate the diagnosis of malignancy.

Table 2. Genetic alterations in primary SS

Biological Consequence

Table 2. Genetic alterations in primary SS

Biological Consequence

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