Extended Data Fig. 10: VCAM1 is broadly expressed across human AML subgroups.
From: VCAM1 confers innate immune tolerance on haematopoietic and leukaemic stem cells
(a-b) Published gene expression microarray data from 183 patients (GSE10358) was analyzed for the expression of VCAM1 across French-American-British (FAB) subgroups of human AML. (a) VCAM1 is broadly expressed across all FAB AML subgroups with the highest expression on the M6 subgroup. (b) Association between VCAM1 expression and human AML mutations. The only statistically significant difference detected was a lower expression of VCAM1 in NPM1 mutated AML compared to the others. DNMT3A, mutation of the DNMT3A gene; FLT3-ITD, internal tandem duplication of the FLT3 gene; FLT3-TKD, tyrosine kinase domain mutation of the FLT3 gene; IDH1 and 2, mutation of the IDH1 and 2 genes; NPM1, mutation of the NPM1 gene. Box plots: media, whiskers: minimum and maximum. Mann-Whitney test (a, b). (c) VCAM1 gene expression data from sorted human AML BM samples and healthy controls (GSE35008 and GSE35010). Lineage− CD34+ CD38− CD90+ cells (referred to as LT-HSCs), Lineage− CD34+ CD38− CD90− cells (referred to as ST-HSCs), and Lineage− CD34+ CD38+ CD123+ CD45RA+ cells (referred to as GMPs). Cytogenetic abnormalities are depicted as: NK, normal karyotype; CK, complex karyotype; 7q, deletion of chromosome 7 (LT-HSCs healthy, NK, 7q n = 4, CK n = 5; ST-HSCs healthy,7q n = 6, NK, CK n = 4; GMP healthy, 7q n = 6, NK n = 4, CK n = 5 human samples). Box plots: media, whiskers: minimum and maximum. One-way ANOVA analyses followed by Tukey’s multiple comparison tests (c). (d) Representative flow-cytometry plots depicting the phagocytosis of human #V6 AML sample by human CD14+ monocytes when treated with anti-VCAM1, compared with the IgG1 control. CTFR, cell trace far red. (e) Percentage of live human CD45+ AML cells in the blood of leukaemic mice comparing pre- and post-treatment (IgG1 control (n = 10 biological replicates) or anti-human VCAM1 antibody (n = 9 biological replicates). Data from the mice in Figs. 5i and j. Significant P values are indicated in the figure.
