Genetics- and immune-related factors in the pathogenesis of lymphoplasmacytic lymphoma/ Waldenström's macroglobulinemia

Abstract

There are emerging data to support a role for genetic and immune-related factors in the pathogenesis of lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia. In this article, we review our recently published, large, population-based studies using data from Sweden and from United States veterans and propose mechanisms and pathways underlying our observations. We also discuss future directions for new studies designed to increase our current knowledge and to define underlying biologic mechanisms of our findings. Finally, based on novel insights on this topic, we discuss clinical implications and provide perspective on the relevance of these data for patient counseling and clinical follow-up.

Figure 1

The normal steps in B-cell maturation. WM is considered to originate from cells that have been through the process of somatic hypermutation at the lymph node but have not yet undergone isotype class switching. Both genetic susceptibility and sustained antigenic stimulation, which can be observed during autoimmunity and chronic infection, constitute risk factors for WM development. (Adapted from Ghobrial et al, Lancet Oncol 2003.)