What happens after the neoplastic CLL transformation?
The view currently given most credence is that CLL represents a single disease presumably originating from the neoplastic transformation of marginal zone T-cell independent B lymphocytes at different steps during activation.3,95 This working hypothesis has been substantiated by independent studies in which 2 types of CLL were shown to have largely overlapping genetic profiles,96,97 although they are distinguished by a different mutational status of the IgV genes that may account for phenotypic differences. The preferential presence of the activation marker CD38 in unmutated cases may imply that these cells are exposed to the antigen, although in such a way as to initiate the activation process without inducing somatic hypermutation. According to this hypothesis, the antigens recognized by these BCRs would likely be carbohydrate components of bacterial and viral origin and mimicking self-antigens (and would thus always be present at low concentrations). The findings of low affinities an
