Conserved RELA dependency in patient-derived MPN mouse models. (A) Schematic of the primary sample models and downstream assays after RELA perturbation. (B) Colony assay of CD34⁺ cells after RELA knockout (KO). Representative images (left). Relative numbers (right, n = 3 biological replicates). Statistics were assessed by 2-tailed Student’s t test. (C) Relative colony numbers after RELA knockout from additional unique patients with MPN (n = 5) and NBM donors (n = 5). Statistics were assessed by 2-tailed Student’s t test comparing MPN and NBM after taking an average of each 3 biological replicates per sample. (D-I) Leukemic engraftment in the PB, BM at end point, normalized spleen weights, survival curves, and BM histology in the 298181 primary MF (D-E; n = 5 mice per group), 530675 primary MF (F-G; n = 5 mice for control, n = 4 for RELA^KO), and NBM1 (H-I; n = 4 mice for control, n = 5 for RELA^KO) PDX models. PB human CD45⁺ (hCD45⁺) cells statistics assessed by 2-way ANOVA. BM hCD45⁺ and normalized spleen weights statistics assessed by 2-tailed Student t test. Survival curves assessed by log-rank test. Scale bar = 75 μm. (J) Gene set enrichment analysis scores after RNA sequencing analysis of 4 paired MPN samples after RELA knockout. (K) Expression of pertinent genes from RNA sequencing data after RELA knockout. Statistics assessed by Wilcoxon matched-pairs signed rank test. ns, nonsignificant; X, no data.