Cell cycle and apoptosis deregulation in classical Hodgkin lymphomas.
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)-kappaB 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 I4P 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.
Bai
Maria
M
Department of Pathology, Medical Faculty, University of Ioannina, Ioannina, Greece. mbai@cc.uoi.gr
Papoudou-Bai
Alexandra
A
Kitsoulis
Panagiotis
P
Horianopoulos
Nikolaos
N
Kamina
Sevasti
S
Agnantis
Niki John
NJ
Kanavaros
Panagiotis
P
D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D020031:Epstein-Barr Virus Infections / Q000150:complications; D004854:Herpesvirus 4, Human / Q000502:physiology; D006689:Hodgkin Disease / Q000473:pathology* / Q000821:virology; D006801:Humans; D016539:Reed-Sternberg Cells / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology