Data di Pubblicazione:
2012
Abstract:
Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin's lymphoma found in children and young adults. ALCLs frequently carry a chromosomal translocation that results in expression of the oncoprotein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). The key molecular downstream events required for NPM-ALK-triggered lymphoma growth have been only partly unveiled. Here we show that the activator protein 1 family members JUN and JUNB promote lymphoma development and tumor dissemination through transcriptional regulation of platelet-derived growth factor receptor-β (PDGFRB) in a mouse model of NPM-ALK-triggered lymphomagenesis. Therapeutic inhibition of PDGFRB markedly prolonged survival of NPM-ALK transgenic mice and increased the efficacy of an ALK-specific inhibitor in transplanted NPM-ALK tumors. Notably, inhibition of PDGFRA and PDGFRB in a patient with refractory late-stage NPM-ALK(+) ALCL resulted in rapid, complete and sustained remission. Together, our data identify PDGFRB as a previously unknown JUN and JUNB target that could be a highly effective therapy for ALCL.
Tipologia CRIS:
03A-Articolo su Rivista
Elenco autori:
Laimer D;Dolznig H;Kollmann K;Vesely PW;Schlederer M;Merkel O;Schiefer AI;Hassler MR;Heider S;Amenitsch L;Thallinger C;Staber PB;Simonitsch-Klupp I;Artaker M;Lagger S;Turner SD;Pileri S;Piccaluga PP;Valent P;Messana K;Landra I;Weichhart T;Knapp S;Shehata M;Todaro M;Sexl V;Höfler G;Piva R;Medico E;Ruggeri BA;Cheng M;Eferl R;Egger G;Penninger JM;Jaeger U;Moriggl R;Inghirami G;Kenner L
Link alla scheda completa:
Link al Full Text:
Pubblicato in: