Molecular pathogenesis of Hodgkin lymphoma

Hodgkin lymphoma (HL) is a distinctive lymphoma subtype that accounts for approximately 30% of all lymphomas in the Western world and approximately 5% in Japan. HL is characterized by the giant multinucleated tumor cells called Hodgkin/Reed-Sternberg (H/RS) cells, but the cellular origin had long been unknown. Recent investigations have clarified that H/RS cells have a clonally rearranged immunoglobulin gene in most cases, but it still seems appropriate to differentiate HL from other B-cell neoplasms, because the transforming event rather than its cellular origin is more likely to influence the nature of H/RS cells. Many questions remain to be answered for comprehensive understanding of the pathogenesis of HL. The presence of H/RS cells alone is probably not enough for disease onset, but the immune reaction against these cells appears to be inevitable for generation of HL. Most HL patients are cured with current treatment strategies, but some of them have refractory or recurrent disease, and intensified treatment occasionally induces therapy-related secondary malignancies. Because the growth and survival of H/RS cells are supported by various external stimuli and constitutive intracellular signals, management of HL is expected to be one of the best applications of molecule-targeted therapy.