FIGURE 1 from Siglec-15 Promotes Evasion of Adaptive Immunity in B-cell Acute Lymphoblastic Leukemia

Abstract

<p>Sig15 is highly expressed in B-ALL and additional hematologic malignancies. <b>A,</b> Relative <i>SIG15</i> expression. B-ALL (<i>N</i> = 147; <i>P</i> = 3.6 × 10<sup>−19</sup>) and AML (<i>N</i> = 542; <i>P</i> = 2.0 × 10<sup>−9</sup>) samples showed higher <i>SIG15</i> than normal PBMC samples (<i>N</i> = 74). Data adapted from Haferlach and colleagues through Oncomine.org (<a href="#bib53" target="_blank">53</a>). <b>B,</b> Relative <i>SIG15</i> expression across a panel of common childhood cancers from the St. Jude PeCan database. Dotted red line indicates median expression for all tumors in the graph (*, <i>P</i> < 0.05; ****, <i>P</i> < 0.0001, ANOVA). Western blot analysis shows higher SIG15 expression across a panel of B-ALL (<b>C</b>), AML (<b>D</b>), and DLBCL human cell lines compared with normal healthy PBMCs (NML). No B-ALL or DLBCL cell lines show detectable levels of the Sig15 binding partner DAP12. SIG15 was probed using the Invitrogen polyclonal antibody. <b>E,</b> Representative flow cytometry of primary childhood B-ALL. Three of seven BMA samples had B-ALL cells which stained positive/dim-positive for Sig15 and one of eight PBL samples had B-ALL cells which stained positive. Zero of two hematogones from non-leukemia donor BMA samples and zero of six B cells from PBL samples from non-leukemia donors were positive for Sig15. Dotted lines represent the mean fluorescence intensity from normal hematogones and B cells. SIG15 was probed using the NP159 mAb (NextCure) conjugated to Alexa Fluor 647.</p>