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. 2021 Nov 17;12(2):388–401. doi: 10.1158/2159-8290.CD-21-0410

Figure 6.

Figure 6. IL15 overexpression is associated with resistance to FLT3i in FLT3-ITD+ cells. A, Hierarchical clustering of FLT3-ITD–positive AML patient samples and six FLT3i resulted in two groups of the samples with high (sensitive group) and low (resistant group) efficacy to FLT3 inhibitors (FLT3i). B, Differential gene expression of FLT3i-sensitive versus FLT3i-resistant samples depicts upregulation of the IL15, CD14, and CD300E genes in the FLT3i-resistant group. C, The overexpression of IL15 was significant in FLT3-ITD–mutant FLT3i-resistant samples in our data and in the Beat AML data set. D, Gene set enrichment analysis of the genes upregulated in FLT3i-resistant samples depicts the MAPK pathway as the top enriched pathway. E, AML patient cells stimulated with human recombinant IL15 had increased phosphorylation of ERK compared with unstimulated control cells using phospho-flow cytometry. The color bar displays phosphorylation ratio to the control cells. F, FLT3i sensitivity and expression of IL15 in serial samples from the patient AML_129. G, The UMAP plots demonstrate expression of IL15 and IL15 receptor (IL15RA) in eight AML patient samples from published study (Dufva et al.; ref. 37).

IL15 overexpression is associated with resistance to FLT3i in FLT3-ITD+ cells. A, Hierarchical clustering of FLT3-ITD–positive AML patient samples and six FLT3i resulted in two groups of the samples with high (sensitive group) and low (resistant group) efficacy to FLT3 inhibitors (FLT3i). B, Differential gene expression of FLT3i-sensitive versus FLT3i-resistant samples depicts upregulation of the IL15, CD14, and CD300E genes in the FLT3i-resistant group. C, The overexpression of IL15 was significant in FLT3-ITD–mutant FLT3i-resistant samples in our data and in the Beat AML data set. D, Gene set enrichment analysis of the genes upregulated in FLT3i-resistant samples depicts the MAPK pathway as the top enriched pathway. E, AML patient cells stimulated with human recombinant IL15 had increased phosphorylation of ERK compared with unstimulated control cells using phospho-flow cytometry. The color bar displays phosphorylation ratio to the control cells. F, FLT3i sensitivity and expression of IL15 in serial samples from the patient AML_129. G, The UMAP plots demonstrate expression of IL15 and IL15 receptor (IL15RA) in eight AML patient samples from published study (Dufva et al.; ref. 37).