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. 2024 Aug 6;32(5):582–600. doi: 10.4062/biomolther.2024.017

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Copyright © 2024, The Korean Society of Applied Pharmacology

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Fig. 1 — Tumoral VISTA in CML patients and cells is involved in TKI resistance and poor survival. (A) Scatter plot showing the relative expression of VSIR in K562 cells resistant to 2 μM IM (n=8) compared with K562 cells resistant to 0.5 μM IM (n=8) and K562 cells (n=8) based on the GSE203442 dataset (p<0.05). (B) The relative expression of VSIR in K562 cells resistant to TKIs (K562-R cells, n=3) compared with that in K562 cells (n=3) was analyzed in GSE208314 (p<0.05). (C) VSIR expression in the GSE44589 dataset was lower in IM-treated patients (n=63) than in untreated CML patients (n=135) (p<0.05). (D) There were 183 CML patients who received IM treatment in the GSE130404, GSE44589 and GSE33224 datasets, among which 124 patients achieved a drug response (IM-R) and 59 patients showed no response (IM-NR). A heatmap of the differential gene expression between IM-R and IM-NR and the top 50 upregulated genes and the top 50 downregulated genes are shown (red indicates upregulated genes; blue indicates downregulated genes). (E) The abscissa indicates the gene ratio, and the enriched pathways are presented on the ordinate. GO analysis of potential targets of DGE between IM-R and IM-NR based on the Cluster Profiler package in R software (version: 4.3.2). Colors represent the significance of differential enrichment, and the size of the circles represents the number of genes; the larger the circle is, the greater the number of genes. According to the enrichment results, p<0.05 or FDR <0.05 was considered to indicate a meaningful pathway (an enrichment score of −log10 (P) greater than 1.3). (F) The GSE51082 dataset was used to verify VSIR mRNA levels in hematologic malignancies, and the scatter plot shows that the levels of VSIR expression were greater in AML (n=37), CML (n=22) and MDS (n=10) than in T-ALL (n=13), Pre-B-ALL (n=17) and B-CLL (n=41) (p<0.001). (G) Survival time of AML patients with different expression levels of VSIR (log-rank p<0.001). Asterisks (*) indicate significance, *** indicates p<0.001, and * indicates p<0.05.