title: 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)-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.
authors.affiliation: Department of Pathology, Medical Faculty, University of Ioannina, Ioannina, Greece. mbai@cc.uoi.gr
authors.forename: Maria
authors.initials: M
authors.lastname: Bai
authors.forename: Alexandra
authors.initials: A
authors.lastname: Papoudou-Bai
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kitsoulis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Horianopoulos
authors.forename: Sevasti
authors.initials: S
authors.lastname: Kamina
authors.forename: Niki John
authors.initials: NJ
authors.lastname: Agnantis
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kanavaros
mesh_terms: 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