Focusing on NPM1-mutated (NPM1mut) AML as a model23, we here show that the miR-126high cell subpopulation, revealed by an optimized lentiviral miR-126 reporter, enriches for LSCs in xenografts, allowing dynamic LSC monitoring before and after chemotherapy and generation of a transcriptional LSC signature in prospectively isolated LSCs. This evidence concerns the gene NPM1 and acute myeloid leukemia.