Fig. 1: In vitro and in vivo CRISPR screening reveals DDX6 as one of the most promising vulnerabilities in AML.
From: DDX6 undergoes phase separation to modulate metabolic plasticity and chemoresistance
a Schematic representation of in vitro and in vivo CRISPR screenings. Created in BioRender. Bi, H. (2025) https://BioRender.com/5y4p2p4. b–d The normalized median CRISPR scores of the 101 genes in vitro CRISPR screening with Mono-mac-6 AML cells (b), in vitro CRISPR screening with AML PDX cells (c), and in vivo CRISPR screening with AML PDX mouse model (d). e–g Normalized CRISPR scores of the top 5 overlapped genes in vitro CRISPR screening with Mono-mac-6 AML cells (e), in vitro CRISPR screening with AML PDX cells (f), and in vivo CRISPR screening with AML PDX mouse model (g). Data are the mean ± SEM of n = 24 (Positive control), 40 (Negative control), and 20 (EIF5A, DDX6, CNOT3, EIF4E, PABPC1) independent sgRNAs. Simple one-way ANOVA. Box plots show the median (center line), the first and third quartiles (bounds of the box). Whiskers are chosen to show 1.5 of the Interquartile Range. h The PS-Self scores of the top 5 RBPs. PS-Self: self-assembling phase-separating. i The PS-Part score of the top 5 RBPs. PS-Part: partner-dependent phase-separating. j Representative images showing the impact of KO of CNOT3, EIF4E, PABPC1, and DDX6 on PB assembly in Mono-mac-6 AML cells. Green: Dcp1b. k Statistical results of PB numbers in Mono-mac-6 AML cells following CNOT3, EIF4E, PABPC1, and DDX6 KO (n = 11 [sgNS]; 12 [sgDDX6], or 13 [sgPABPC1, sgCNOT3, and sgEIF4E]). l Relative expression levels of DDX6 in various AML subtypes compared to healthy controls. m, n Protein levels of DDX6 in AML cells (m), PDX cells (n), and healthy controls. o Relative growth of Mono-mac-6 AML cells following DDX6 KO. p Relative growth of AML PDX cells following DDX6 KO and overexpression (OE). sgDDX6-1 was utilized for (j and p). o and p: mean ± SEM (n = 3 independent experiments); m and n: n = 3 independent experiments with consistent results; Unpaired two-tailed Student’s t-test was utilized for all analyses. Source data are provided as a Source Data file.
