The biology of Hodgkin's lymphoma

Abstract

Hodgkin and Reed–Sternberg (HRS) cells of classical Hodgkin's lymphoma are probably derived from germinal centre B cells that have acquired disadvantageous immunoglobulin variable chain gene mutations and normally would have undergone apoptosis, whereas lymphocytic and histiocytic (L&H) cells of NLPHL appear to derive from antigen-selected germinal centre B cells. Few cases of classical Hodgkin's lymphoma originate from T cells. Classical Hodgkin's lymphoma is unique among human lymphomas in the extent to which the lymphoma cells have undergone reprogramming of gene expression. They have lost expression of most B cell-typical genes and acquired expression of multiple genes that are typical for other types of cells of the immune system. Multiple signalling pathways and transcription factors show deregulated activity in HRS cells, including nuclear factor-κB, Jak–Stat, PI3K–Akt, Erk, AP1, notch 1 and receptor tyrosine kinases. The transforming events involved in the generation of HRS cells are only partly understood, but several known recurrent genetic lesions involve members of the nuclear factor-κB or Jak–Stat signalling pathways. HRS cells attract many cells into the lymphoma tissue, resulting in a typical inflammatory microenvironment. This environment probably promotes the survival of HRS cells and helps them to escape attack from cytotoxic T or natural killer cells.