Fig. 3: CR fusion cooperates with oncogenic RAS to drive myeloid malignancy.

a Diagram of concurrent mutations with RARG fusions in RARG-AML. b Schematic of the double mutation mouse model. c Survival curves of recipients transplanted with the indicated cells. Statistical analysis was performed by Log-rank test. d Flow cytometry analysis of GFP⁺ cells in the BM (CRS/N, n = 4 mice) and spleen of recipients. BM and spleen: WT groups, n = 5 mice/group; CRL/CRS groups, n = 6 mice/group. e Flow cytometry qualification the proportion of Mac1⁺Gr1^‒ cells among GFP⁺ cells in WT/N and CR/N mice. Spleen WT groups, n = 3 mice/group; other groups, n = 5 mice/group. f Representative pictures of spleen and statistical results of spleen and liver weight. n = 6 mice/group. g Representative H&E staining of BM, spleen and liver sections, and Wright-Giemsa staining of BM cytospins of recipients. Scale bars, 100 μm for tissue section and 5 μm for BM cytospins. The images are representative of 3 mice/group. h UMAP displaying seven distinct cell populations in the BM cells of recipients, including hematopoietic stem cell/multipotent progenitor (HSC/MPP), common myeloid progenitor (CMP), granulocyte and monocyte progenitor (GMP), pro-monocyte (pro-mono), monocyte (mono), early differentiation stage granulocyte (early_GN), and late differentiation stage granulocyte (late_GN). i Leukemic cell population was defined by human NRAS expression. j The re-clustered leukemic cell subsets. k The proportion of leukemic subsets in WT/N and CR/N mice. l–m The enriched gene set enrichment analysis (GSEA) terms for CRL/N (l) and CRS/N (m), in comparison to WT/N, were identified within leukemia clusters C2 to C4. The P-value is calculated via two-tailed permutation test. All the data are shown as the mean ± SD, statistical analysis was performed by two-tailed one-way ANOVA with Tukey’s multiple comparisons test (d–f). See also Supplementary Fig. 4. Source data are provided as a Source Data file.