Origin of Non-Hodgkin Lymphoma and Therapeutic Targets
Non-Hodgkin lymphoma is the most common type of blood cancer. Over the past 2 decades, discoveries in basic immunology and the pathogenesis of malignancies have significantly advanced our understanding of the origin of lymphoid neoplasms. These diseases have been reexamined and grouped based on recurrent chromosomal rearrangements, histologic patterns, and gene expression profiles. The multiple revisions to the World Health Organization’s classification schemes for lymphomas reflect this progress. As with other cancers, lymphoma development is dependent upon acquisition of mutations, DNA copy number changes, recurrent cytogenetic rearrangements, and epigenetic dysregulation of gene expression involving oncogenic and tumor suppressor pathways. Many of these derangements occur as a result of disordered genetic recombination and somatic hypermutation events intended to support adaptive immunity. Also, analysis of molecular features of lymphomas compared to normal lymphocyte compartments provides clues to the events driving their pathogenesis.
