American Association for Cancer Research
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FIGURE 1 from Siglec-15 Promotes Evasion of Adaptive Immunity in B-cell Acute Lymphoblastic Leukemia

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posted on 2023-07-17, 14:20 authored by Claire E. Pillsbury, Jodi Dougan, Jennifer L. Rabe, Jairo A. Fonseca, Chengjing Zhou, Alyssa N. Evans, Hasan Abukharma, Ona Ichoku, Gloria Gonzalez-Flamenco, Sunita I. Park, Ahmed Aljudi, Deborah DeRyckere, Sharon M. Castellino, Sarwish Rafiq, Solomon Langermann, Linda N. Liu, Curtis J. Henry, Christopher C. Porter

Sig15 is highly expressed in B-ALL and additional hematologic malignancies. A, Relative SIG15 expression. B-ALL (N = 147; P = 3.6 × 10−19) and AML (N = 542; P = 2.0 × 10−9) samples showed higher SIG15 than normal PBMC samples (N = 74). Data adapted from Haferlach and colleagues through (53). B, Relative SIG15 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 (*, P < 0.05; ****, P < 0.0001, ANOVA). Western blot analysis shows higher SIG15 expression across a panel of B-ALL (C), AML (D), 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. E, 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.


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CURE Childhood Cancer (CURE)

Alex's Lemonade Stand Foundation for Childhood Cancer (ALSF)

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We demonstrate that Sig15 is overexpressed in hematologic malignancies driven by NFκB, is required for immune evasion in a mouse model of leukemia, and, for the first time, that it circulates at high levels in the plasma of children with leukemia.