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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).
Abstract Abnormal metabolism is a fundamental hallmark of cancer and represents a therapeutic opportunity, yet its regulation by oncogenes remains poorly understood. Here, we uncover that JMJD1C, a jumonji C (JmjC)-containing H3K9 demethylase, is a critical regulator of aberrant metabolic processes in homeobox A9 (HOXA9)-dependent acute myeloid leukemia (AML).
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