• Targeting RSPO3-LGR4 Signaling for Leukemia Stem Cell Eradication in Acute Myeloid Leukemia.

Targeting RSPO3-LGR4 Signaling for Leukemia Stem Cell Eradication in Acute Myeloid Leukemia.

Cancer cell (2020-06-20)
Basit Salik, Hangyu Yi, Nunki Hassan, Nancy Santiappillai, Binje Vick, Patrick Connerty, Alastair Duly, Toby Trahair, Andrew J Woo, Dominik Beck, Tao Liu, Karsten Spiekermann, Irmela Jeremias, Jianlong Wang, Maria Kavallaris, Michelle Haber, Murray D Norris, Dan A Liebermann, Richard J D'Andrea, Christopher Murriel, Jenny Y Wang

Signals driving aberrant self-renewal in the heterogeneous leukemia stem cell (LSC) pool determine aggressiveness of acute myeloid leukemia (AML). We report that a positive modulator of canonical WNT signaling pathway, RSPO-LGR4, upregulates key self-renewal genes and is essential for LSC self-renewal in a subset of AML. RSPO2/3 serve as stem cell growth factors to block differentiation and promote proliferation of primary AML patient blasts. RSPO receptor, LGR4, is epigenetically upregulated and works through cooperation with HOXA9, a poor prognostic predictor. Blocking the RSPO3-LGR4 interaction by clinical-grade anti-RSPO3 antibody (OMP-131R10/rosmantuzumab) impairs self-renewal and induces differentiation in AML patient-derived xenografts but does not affect normal hematopoietic stem cells, providing a therapeutic opportunity for HOXA9-dependent leukemia.

Product Number
Product Description

CRISPR/Cas9 Products and Services, Design and order CRISPR gRNA, Cas9, screening libraries, controls and companion products. Formats include plant, lentivirus, IVT-RNA, plasmid, synthetic, and protein.
Anti-phospho-CREB (Ser133) Antibody, Upstate®, from rabbit
Anti-Actin antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
MISSION® esiRNA, targeting human LGR4
CRISPR-Lenti Non-Targeting Control Plasmid
MISSION® esiRNA, targeting mouse Lgr4
MISSION® TRC2 pLKO.5-puro Non-Target shRNA Control Plasmid DNA, Targets no known genes from any species