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. 2023 May 16;13(8):1922–1947. doi: 10.1158/2159-8290.CD-22-1396

Figure 6.

Figure 6. Higher IL3Rα/βc ratios bias hexamer signaling to promote leukemia stemness programs. A, GSVA showing hexamer versus dodecamer signature enrichment in AML FAB subtypes [The Cancer Genome Atlas (TCGA), Beat AML, and Leucegene; refs. 25, 26, 57]. B, GSVA plot showing enrichment of the hexamer vs. dodecamer signature in FLT3-ITD– and RUNX1-mutant AML patients (Beat AML and TCGA; refs. 25, 26). Dod, dodecameric; Hex, hexameric; NES, normalized enrichment score. C, GSEA plot showing downregulated genes from IL3Rα/βc-high transcript ratio AML patient samples are enriched in the downregulated genes in the hexamer gene signature. D, Hexamer vs. dodecamer signature GSVA scores in the immunophenotypically characterized primary AML patient samples with high (indicated in blue) and low (indicated in red) IL3Rα/βc transcript ratio (Toronto cohort). E, Schematic for generation of the intersect hexamer and dodecamer gene signatures linking IL3Rα/βc cell-surface protein ratio and hexamer vs. dodecamer signaling. F, GSVA demonstrating the enrichment of the intersect hexamer vs. dodecamer signature in AML patient samples with primitive cellular hierarchy (32). G, GSVA plot showing enrichment of the intersect hexamer vs. dodecamer signature in more primitive fractions (as defined by CD34 CD38 expression) from primary AML patient samples (n = 110 RNA-seq; ref. 32). H, GSVA plot showing enrichment of the intersect hexamer vs. dodecamer signature in stem and progenitor cells in the leukemia cellular hierarchy (32, 35). I, Enrichment of the intersect hexamer vs. dodecamer signature in more primitive sorted populations from CB (36, 37). CMP, common myeloid progenitors; GMP, granulocyte-monocyte progenitors; Gr, granulocytes; HSC, hematopoietic stem cells; MEP, megakaryocyte-erythroid progenitors; MLP, multilymphoid progenitors; Mono, monocytes; MPP, multipotent progenitors. J, The intersect hexamer vs. dodecamer signature (GSVA) is enhanced in LSC+ (engrafting) over LSC− (nonengrafting) fractions (32). K, Enrichment of the intersect hexamer vs. dodecamer signature in patients with higher LSC frequency compared with nonengrafting (NE) fractions (20).

Higher IL3Rα/βc ratios bias hexamer signaling to promote leukemia stemness programs. A, GSVA showing hexamer versus dodecamer signature enrichment in AML FAB subtypes [The Cancer Genome Atlas (TCGA), Beat AML, and Leucegene; refs. 25, 26, 57]. B, GSVA plot showing enrichment of the hexamer vs. dodecamer signature in FLT3-ITD– and RUNX1-mutant AML patients (Beat AML and TCGA; refs. 25, 26). Dod, dodecameric; Hex, hexameric; NES, normalized enrichment score. C, GSEA plot showing downregulated genes from IL3Rα/βc-high transcript ratio AML patient samples are enriched in the downregulated genes in the hexamer gene signature. D, Hexamer vs. dodecamer signature GSVA scores in the immunophenotypically characterized primary AML patient samples with high (indicated in blue) and low (indicated in red) IL3Rα/βc transcript ratio (Toronto cohort). E, Schematic for generation of the intersect hexamer and dodecamer gene signatures linking IL3Rα/βc cell-surface protein ratio and hexamer vs. dodecamer signaling. F, GSVA demonstrating the enrichment of the intersect hexamer vs. dodecamer signature in AML patient samples with primitive cellular hierarchy (32). G, GSVA plot showing enrichment of the intersect hexamer vs. dodecamer signature in more primitive fractions (as defined by CD34 CD38 expression) from primary AML patient samples (n = 110 RNA-seq; ref. 32). H, GSVA plot showing enrichment of the intersect hexamer vs. dodecamer signature in stem and progenitor cells in the leukemia cellular hierarchy (32, 35). I, Enrichment of the intersect hexamer vs. dodecamer signature in more primitive sorted populations from CB (36, 37). CMP, common myeloid progenitors; GMP, granulocyte-monocyte progenitors; Gr, granulocytes; HSC, hematopoietic stem cells; MEP, megakaryocyte-erythroid progenitors; MLP, multilymphoid progenitors; Mono, monocytes; MPP, multipotent progenitors. J, The intersect hexamer vs. dodecamer signature (GSVA) is enhanced in LSC+ (engrafting) over LSC− (nonengrafting) fractions (32). K, Enrichment of the intersect hexamer vs. dodecamer signature in patients with higher LSC frequency compared with nonengrafting (NE) fractions (20).