Figure 3.

Irf8 represents a PML/RARα-target gene that is refractory to ATRA and ATO signaling. (a) Heatmaps of Irf8-centered dysregulated genes in c-Kit⁺ APL progenitors that were refractory to ATRA or ATO treatment. (b) Mouse APL cells were treated daily with ATRA or ATO alone or in combination for 6 days, and the mRNA expression levels of Meis1, Irf8 and Mef2c were measured by RT-PCR. (c) The subtype-associated mRNA expression profiles of MEIS1,IRF8 and MEF2C among 172 leukemic blast-enriched BM samples of human AML (FAB classification). The raw data were obtained from the The Cancer Genome Atlas AML database and were normalized to the GAPDH mRNA level. (d) Quantitative RT-PCR assay on the expression of Irf8 in the c-Kit⁺ APL progenitors and normal myeloid subsets indicated. (e) PML/RARα was transduced into normal c-Kit⁺ BM cells by retroviral infection, and the mRNA levels of Meis1, Irf8 and Mef2c were measured by RT-PCR. (f) Western blot assay for the protein level of Irf8 in GFP⁺ mouse APL cells with or without ATRA or ATO treatment in vivo. (g) The RT-PCR measurement of IRF8 mRNA levels in primary APL BM blasts treated with or without ATRA (1 μM) or ATO (1 μM) for 72 h in vitro. Normal monocytes and granulocytes were used as control. All data in this figure are presented as the mean±S.D., *P <0.05, **P<0.01