Cell Cycle and Apoptosis Deregulation in Classical Hodgkin Lymphomas

Abstract

Classical Hodgkin lymphomas (cHL) have now been recognized as B-cell lymphomas with some exceptional cases of T-cell origin. In recent years, there has been accumulating evidence that Hodgkin and Reed-Sternberg (H/RS) cells, the presumed neoplastic-cell population in cHL, are characterized by a profound disturbance of the cell cycle and apoptosis regulation. The constitutive activation of the nuclear factor (NF)-kB pathway, which is considered to be involved in the proliferation and survival of H/RS cells. Moreover, substantial evidence that H/RS cells have defective cell cycle and apoptosis regulation has been provided by studies showing that these cells are characterized, in a large proportion of cases, by alterations of the p53, Rb and p27 tumor suppressor pathways, overexpression of cyclins involved in the G1/S and G2/M transition such as cyclins E, D2, D3, A and B1, overexpression of cyclin-dependent kinases such as CDK1, 2 and 6 and overexpression of anti-apoptotic proteins such as c-FLIP, bcl-xl, c-IAP2, X-linked IAP and survivin. Recent studies suggest that interleukin 13 (IL-13) is an important growth and survival factor in H/RS cells. Furthermore, the Epstein-Barr Virus (EBV), which is present in H/RS cells in about 30-50% of cHL, has been shown to affect the cell cycle and apoptosis regulation in cHL. The present review summarizes data with respect to the cell cycle and apoptosis deregulation in cHL.