MUM-1: A STEP AHEAD TOWARD THE UNDERSTANDING OF LYMPHOMA HISTOGENESIS

In recent times, the field of B cell lymphoma histogenesis has progressed rapidly due to the increasing availability of histogenetic markers. Genotypic markers of B cell histogenesis are represented by mutations of IgV and BCL-6 genes, which are somatically acquired at the time of B cell transit through the germinal center (GC). Phenotypic markers are represented by BCL-6 and CD138/syndecan-1 protein expression and allow the distinction between GC and post-GC B cells. On this basis, lymphomas may be histogenetically distinguished into: (1) lymphomas devoid of somatic IgV and BCL-6 hypermutation, which derive from pre-germinal center B cells; (2) lymphomas associated with somatic IgV and/or BCL-6 hypermutation and BCL-6 expression, which closely reflect germinal center B cells; and (3) lymphomas associated with somatic IgV and/or BCL-6 hypermutation, as well as CD138/syndecan-1 positivity, representing lymphomas of post-germinal center B cells. In the March issue of Leukemia, Tsuboi et al report on the expression pattern of MUM1 in normal lymphoid tissues and in lymphoma. Because expression of MUM1 protein appears to be strictly regulated during lymphoid differentiation, and because expression of the molecule is retained upon neoplastic transformation, MUM1 may be added to the panel of phenotypic markers of B cell lymphoma histogenesis. In particular, MUM1 may provide a marker for the identification of transition from BCL-6 positivity (GC B cells) to CD138 expression (immunoblasts and plasma cells). These studies are of potential clinical value, since in some B cell malignancies, histogenesis may influence prognosis.