Figure 4. PML-RARα Drives APL by Impeding PHRF1-Driven TGIF Degradation. See also Figure S4.
(A) U937-MTPR9 cells stably expressing the indicated expression vectors were cultured with Zn for 16 hr before being treated with TGF-β plus vitamin D3 (TGF-β/D3) for 5 days. Cell differentiation was evaluated by determining the number of positive CD14 cells.
(B) NB4 cells were transiently transduced with the indicated combinations of lentiviruses and cultured with or without RA and TGF-β for 5 days. Cell differentiation was evaluated by determining the number of positive CD11b cells.
(C, D) MRP8 blasts were stably transfected with Dox-repressible Flag-PHRF1 or Flag-PHRF1.CA alone or together with HA-TGIF.K130R. Expression of PHRF1 or TGIF was determined by direct immunoblotting (C). MRP8 stable cell lines were transplanted to FVB mice, and survival was recorded in a Kaplan-Meier graph (D).
(E, F) Representative H&E staining pictures of liver and spleen (E) or weights of spleen (F) of mice scarified in (D).