EP300-ZNF384 transactivates IL3RA to promote the progression of B-cell acute lymphoblastic leukemia.

The EP300-ZNF384 fusion gene is an oncogenic driver in B-cell acute lymphoblastic leukemia (B-ALL). In the present study, we demonstrated that EP300-ZNF384 substantially induces the transcription of IL3RA and the expression of IL3Rα (CD123) on B-ALL cell membranes. Interleukin 3 (IL-3) supplementation promotes the proliferation of EP300-ZNF348-positive B-ALL cells by activating STAT5. Conditional knockdown of IL3RA in EP300-ZF384-positive cells inhibited the proliferation in vitro, and induced a significant increase in overall survival of mice, which is attributed to impaired propagation ability of leukemia cells. Mechanistically, the EP300-ZNF384 fusion protein transactivates the promoter activity of IL3RA by binding to an A-rich sequence localized at -222/-234 of IL3RA. Furthermore, forced EP300-ZNF384 expression induces the expression of IL3Rα on cell membranes and the secretion of IL-3 in CD19-positive B precursor cells derived from healthy individuals. Doxorubicin displayed a selective killing of EP300-ZNF384-positive B-ALL cells in vitro and in vivo. Collectively, we identify IL3RA as a direct downstream target of EP300-ZNF384, suggesting CD123 is a potent biomarker for EP300-ZNF384-driven B-ALL. Targeting CD123 may be a novel therapeutic approach to EP300-ZNF384-positive patients, alternative or, more likely, complementary to standard chemotherapy regimen in clinical setting.

The enrichment of sugars and phenols from fast pyrolysis of bamboo via ethanol-Fenton pretreatment.

The high-purity compounds (e.g., sugars and phenols) are important raw materials and chemicals, which can be produced by biomass pyrolysis. However, the direct biomass pyrolysis produces complex compounds and thus inhibiting its large-scale utilization. To increase the yield and enrichment of sugars and phenols, a green coupling process based on ethanol-Fenton pretreatment combined with fast pyrolysis is firstly proposed. The bamboo was effectively separated into the ethanol-Fenton pretreated bamboo (EF-bamboo), lignin-rich fractions, and hemicellulose-degradation intermixtures with the massive removal of inorganic metals via this process. Compared with the fast pyrolysis of raw bamboo, the levoglucosan yield of EF-bamboo increased 5.4 times and the enrichment of sugars improved from 7.6% to 59.7%. Similarly, the yield of monophenols from lignin-rich fractions increased around 0.6 times and the enrichment of monophenols increased from 25.7% to 63.5%. This work provides a green and efficient route to produce high-yield and high-enrichment sugars and phenols.