posted on 2023-07-17, 14:20authored byClaire 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
<p>Sig15 is required for adaptive immune escape in murine B-ALL. qRT-PCR shows genetic knockdown of <i>Siglec15</i> expression in a murine model of B-ALL by shRNA (shSig15; <b>A</b>) or knocked out using CRISPR/Cas9 (Sig15 KO; <b>B</b>). Data are normalized to the expression levels of a non-silencing vector control (shNS) or Cas9-expressing cells without gRNA (Cas9). <b>C</b> and <b>D,</b> Unirradiated WT or <i>Rag1<sup>−</sup><sup>/</sup><sup>−</sup></i> C57BL6 mice were injected via tail vein with 5 × 10<sup>5</sup> control or Sig15-deficient leukemia cells. Luciferase signal over time represents disease burden as measured via IVIS imaging over 14 days. Kaplan–Meier curve shows prolonged survival of WT recipients of Sig15-deficient leukemia. <b>E,</b><i>P</i> < 0.0001; shNS WT versus shSig15 WT, Mantel–Cox log-rank test; <i>n</i> = 10 per group from two independent experiments. <b>F,</b><i>P</i> < 0.0001, Cas9-only WT versus Sig15 KO WT; <i>n</i> = 10 per group from two independent experiments.</p>
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)
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.