FOXO1 is a tumor suppressor in classical Hodgkin lymphoma
Menée in vitro, cette étude suggère que le facteur de transcription FOXO1 joue un rôle de suppresseur de tumeurs dans le lymphome de Hodgkin classique
The FOXO transcription factors control proliferation and apoptosis in different cell types. Their activity is regulated by posttranslational modifications, mainly by the PI3K-PKB pathway, which controls nuclear export and degradation. We show that FOXO1 is highly expressed in normal germinal center (GC) B cells as well as in non-Hodgkin lymphomas (NHL) including follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), mucosa-associated lymphoid tissue non-Hodgkin lymphoma (MALT-NHL), B cell chronic lymphocytic leukemia (B-CLL), and mantle-cell lymphoma (MCL). In contrast, in 31 out of 32 classical Hodgkin lymphoma (cHL) cases, Hodgkin and Reed-Sternberg (HRS) cells were FOXO1 negative. Neoplastic cells of nodular lymphocyte predominant Hodgkin lymphoma (LPHL) were negative in 14 out of 20 cases. FOXO1 was down-regulated in cHL cell lines while it was expressed in NHL cell lines at levels comparable to normal B cells. Ectopic expression of a constitutively active FOXO1 induced apoptosis in cHL cell lines and blocked proliferation, accompanied with cell cycle arrest in the G0/G1-phase. We found that in cHL cell lines FOXO1 is inactivated by multiple mechanisms, including constitutive activation of AKT/PKB and MAPK/ERK kinases and up-regulation of microRNAs miR-96, miR-182, and miR-183. These results suggest that FOXO1 repression contributes to cHL lymphomagenesis.
Blood 2012