Demonstration Of Clonality

Some "transformed" lymphomas and their preceding follicular lymphomas may be clonally unrelated.28,29 However, evidence suggests that most transformed follicular lymphomas are derived from the same clone as the antecedent follicular lymphoma. This was shown in studies that demonstrated identical serum monoclonal proteins from a patient before and after transformation, and by studies showing cytoplasmic immunoperoxidase staining for the same protein in biopsies performed before and after transformation.30 Investigators from Stanford examined paired lymphoma biopsies obtained before and after transformation from follicular to diffuse histology.31 They were able to demonstrate a common clonal origin on the basis of anti-idiotype monoclonal antibody cross-reactivity, concordant immunoglobulin and bcl-2 gene rearrangements, and sequencing of light-chain variable genes. The same group also identified identical mutations of the bcl-6 gene in paired lymphomas that were biopsied before and after transformation.32 Analyses of immunoglobulin VHDJH gene sequences33 and bcl-2 rearrangements at other institutions283435 have also demonstrated that diffuse large B-cell lymphomas may be clonally related to antecedent follicu-lar lymphomas.33

CLL and the subsequent diffuse large B-cell lymphoma are clonally related in many situations,36-39 although the two clones may be genetically unrelated in as many as 50% of cases.36'40'41

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