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 Oncomine.org (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.

Funding

Leukemia and Lymphoma Society (LLS)

CURE Childhood Cancer (CURE)

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

현대자동차그룹 | Hyundai Motor America | Hyundai Hope On Wheels (Hope On Wheels)

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ARTICLE ABSTRACT

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.