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. 2022 Dec 12;37(2):288–297. doi: 10.1038/s41375-022-01785-w

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — A FLT3 downstream causal interaction network. The effect of quizartinib (AC220) on the phosphoproteome and proteome profiles of FLT3^ITD-JMD and FLT3^ITD-TKD cells was mapped on a literature curated signaling network, extracted from the SIGNOR resource [11]. For comparative analysis, for each node, the activation state in both cell line is shown (down-left half for ITD-JMD, and top-right half for ITD-TKD). Activated proteins are marked in red, whereas inhibited ones in blue. Phosphosites are displayed as independent rectangles and are colored according to their phosphorylation state after quizartinib treatment, as indicated in the legend. B Representative western blot showing the inhibition of canonical FLT3 downstream targets, as revealed by their phosphorylation status: Tyr694 in STAT5 and Thr202 and Tyr204 in ERK1/2. ITD-JMD and ITD-TKD BaF3 cells were treated for 1.5 h with FLT3 inhibitors treatment (AC220: quizartinib, PKC412: midostaurin and ASP2215: gilteritinib). C Heatmap displaying the enrichment score of GO Biological processes and KEGG pathways significantly (FDR < 0.05) over- (red color) or under- (blue color) represented in the relative dataset (transcripts, proteins and phosphosites in FLT3^ITD-JMD (in blue) and FLT3^ITD-TKD (in orange) BaF3 cells upon quizartinib (AC220) treatment. D, E Boxplots showing the relative abundance of significantly modulated transcripts, proteins and phosphoproteins involved in apoptosis (D) or DNA replication process (E) in BaF3 cells expressing FLT3^ITD-JMD (in blue) and FLT3^ITD-TKD (in orange) upon quizartinib (AC220) treatment.