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. Author manuscript; available in PMC: 2022 Sep 1.
Published in final edited form as: Nat Cell Biol. 2022 Feb 24;24(3):290–298. doi: 10.1038/s41556-022-00849-4

Figure 5. High VCAM1 expression correlates with poor prognosis in human AML.

Figure 5.

(a) Kaplan-Meier survival of AML patients with high (red) and low (blue) VCAM1 expression (mRNA expression z-Score threshold ±2; TCGA Research Network). (b) Experimental strategy. MOLM-13 cells were transduced with a human VCAM1-ZsGreen-expressing (hVCAM1) or ZsGreen control (Mock) lentivirus and transplanted into NOD-scid Il2rg−/− (NSG) mice. (c) Human VCAM1 expression on Mock- and hVCAM1-MOLM-13 cells. (d) Percentage of human CD45+ AML cells in the blood of MOLM-13 transplanted mice (Mock n=8; hVCAM1 n=10 biological replicates). (e) Survival analysis of mice receiving Mock- (n=9 biological replicates) and hVCAM1-MOLM-13 cells (n=10 biological replicates). (f) Survival analysis of mice with established hVCAM1-MOLM-13 AML (>1% peripheral human CD45+ cells) and treated with IgG1 (n=6 biological replicates) and anti-human VCAM1 monoclonal antibody (n=9 biological replicates) for 10 days. (g) In vitro phagocytosis of Mock-MOLM-13 and hVCAM1-MOLM13 cells, in the presence of anti-VCAM1 blocking antibody or IgG1. Values were normalized to the maximum number of events across technical replicates (n=5 biological replicates). (h) In vitro phagocytosis of 3 VCAM1+ human primary AML samples in the presence of anti-VCAM1 blocking antibody or IgG1. Values were normalized to the maximum number of events across technical replicates (n=3 for #V6 and n=6 for #V7–8 patient samples). (i) NSG mice were transplanted with primary human AML and upon disease establishment were daily injected with IgG1 (n=10 biological replicates) or anti-human VCAM1 antibody (n=9 biological replicates) for 10 days. Mice went through two rounds of treatment. Percentage of human CD45+ AML cells in the blood of leukaemic mice comparing pre- and post-treatment. (j) Survival of leukaemic mice treated in (i). (k) Cooperative anti-phagocytic activity of VCAM1 and MHC-I enabling “don’t-eat-me” or “kill-me” activity. VCAM1-mediated interactions between HSCs/LSCs and phagocytes allow PIR-B engagement and immune recognition as self. Error bars, mean ± s.e.m. Box plots: media, whiskers: minimum and maximum. Unpaired two-tailed student’s t test (d, h). Two-way ANOVA with multiple comparisons correction (g). Paired t test (i). Log-rank analysis was used for the Kaplan-Meier survival curves in (a, e, f, j). Significant P values are indicated in the figure.