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Additional file 6: Table S3. Univariate and multivariate analysis for overall survival duration.

Additional file 5: Table S2. The CR rate of AML with different burdens of IKZF1 mutation.

Additional file 4: Table S1. IKZF1-mutated AML patients in our cohort.

Additional file 9: Table S6. The influence of IKZF1 mutation on AML with different SF3B1-mutated status.

Additional file 8: Table S5. The influence of IKZF1 mutation on AML with different CEBPA-mutated status.

Additional file 7: Table S4. The influence of IKZF1 mutation on AML with different CSF3R-mutated status.

Additional file 2. Figure S1. Bone marrow smear diagram and representative images of AML subtypes; Figure S2. Distribution of dual-center test dataset in the study; Figure S3. AMLnet diagnostic pipeline; Figure S4. Performance of the AMLnet on image and patient level in the test set; Figure S5. Visualization of AMLnet Gradients in Discriminating AML Subtypes M1, M2a, M2b, and M4; Table S1. Characteristics of patients in the developmental and dual-center test datasets; Table S2. Subtype-wise performance of AMLnet at the image level on the test set

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. AML patients with FLT3 mutations tend to have a high relapse rate and poor outcome, so FLT3 gene has become an important target for AML treatment, and a series of FLT3 inhibitors have been developed. According to the characteristics of FLT3 inhibitors, they can be divided into first-generation FLT3 inhibitors and second-generation FLT3 inhibitors. So far, totally eight FLT3 inhibitors have been undergone clinical trials and only three were approved for the treatment of AML patients, including Midostourin, Quizartinib and Gilteritinib. FLT3 inhibitors can improve the response rate of patients by combining with standard chemotherapy; in the follow-up maintenance treatment, FLT3 inhibitors can also reduce the disease recurrence rate and improve the overall prognosis of patients. However, the primary drug resistance caused by the bone marrow microenvironment, as well as secondary resistance caused by other mutations may result in poor efficacy of FLT3 inhibitors. For such patients, the combination of FLT3 inhibitor with other drugs may reduce the occurrence of drug resistance and improve the subsequent efficacy of patients. This article reviews the current status of FLT3 inhibitors in clinical research of AML patients and the treatment of FLT3-resistant patients to provide reference for clinicians.

Additional file 1: Figure. S1 Outcomes for patients with p210 stratified by treatment protocols (A) Overall survival (OS) and (B) Disease-free survival (DFS). Figure. S2 4 Single-cell RNA-seq analysis. A, tSNE plot of 17,111 cells, colored by the origin samples (top) and cell types (bottom). B, Expression of marker genes for the normal cell types defined above each panel. C, Barplot of ratios of cells in each cell type. D, Violin plots of top 6 upregulated and downregulated differentially expressed genes between two samples among Tumor cells. E, Dotplot of top 10 enriched GO terms of Tumor cells. Enrichment analysis used significantly differentially expressed genes (|log2FC| > 1.5, p value < 0.05 ) between two samples. F, Dotplot of top 10 enriched KEGG pathways of Tumor cells. Enrichment analysis used significantly differentially expressed genes (|log2FC| > 1.5, p value < 0.05 ) between two samples. G, Differences in GO scored by GSEA between b190 and b210 samples��� Tumor cells. H, Differences in KEGG pathways scored by GSEA between b190 and b210 samples��� Tumor cells.