Highlights • RSPO-LGR4 is essential for stem cell self-renewal in a subset of AML • LGR4 promotes aberrant self-renewal through cooperation with HOXA9 • RSPO3 acts as a stem cell growth factor to sustain proliferation of AML patient blasts • Clinical-grade anti-RSPO3 impairs LSC self-renewal in patient-derived xenografts Summary Signals driving aberrant self-renewal in the heterogeneous leukemia stem cell (LSC) pool determine aggressiveness of acute myeloid leukemia (AML).
