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Journal: bioRxiv
Article Title: A Highly Efficient and Faithful MDS Patient-Derived Xenotransplantation Model for Pre-Clinical Studies
doi: 10.1101/265082
Figure Lengend Snippet: MISTRG replicate granulocytic and megakaryocytic differentiation in response to inhibition of mutant IDH2. In vivo treatment of mutant IDH2 R140Q in MDS-EB-2 (Y021) engrafted MISTRG mice with the IDH2 MUT inhibitor enasidenib. ( a ) Representative histologic images of vehicle (n=8, left) and enasidenib (n=6, right) treated mice engrafted with MDS-EB-2 (Y021). IHC stains for huCD45, huCD68, huCD15, and huCD61 (scale bars 10μm, original magnification 60X). ( b ) Representative FACS plots showing myeloid maturation in response to enasidenib and quantitation of huCD15+ and huCD11b+ expression in vehicle versus enasidenib treated MISTRG mice. ( c ) Comparison of human engraftment in BM from vehicle (n=8) and enasidenib (n=6) treated MISTRG mice. ( d ) Quantitation of huCD41+ expression in PB and BM from vehicle (n=8) and enasidenib (n=6) treated MISTRG mice ( e ) Quantitation of D-2HG in plasma of pre- and post-administration of Vehicle or Enasidenib. Individual mice are represented by symbols with mean ± S.E.M.; statistics represent Mann Whitney test; n.s. not significant, *p<0.05, **p<0.01 for aggregate NSG vs. MISTRG. ( f ) Representation of VAFs of driver mutations in vehicle (left) or enasidenib (right) treated MISTRG (y-axis) plotted against the patient’s VAFs (x-axis). Individual mice represented by symbol shape, mutations color coded. Linear regressors, pearson correlations and p-values between patient and xenograft VAF are displayed.
Article Snippet: To generate isogenic wildtype and mutant expressing cell lines the
Techniques: Inhibition, Mutagenesis, In Vivo, Quantitation Assay, Expressing, MANN-WHITNEY