Acute myeloid leukemia (AML) is characterized by leukemia stem cells (LSCs) that drive disease propagation and relapse. This study prospectively identifies LSCs in AML patients and xenografts using single-cell RNA sequencing and a microRNA-126 reporter. By analyzing NPM1 mutations or chromosome 7 monosomy, LSCs are distinguished from regenerating hematopoiesis, and their longitudinal response to chemotherapy is assessed. Chemotherapy induced inflammation and senescence. Heterogeneity within progenitor AML cells was observed, with some proliferating and differentiating, while others displayed stemness and quiescence features. miR-126(high) LSCs were enriched in chemotherapy-refractory AML and relapse, and their transcriptional signature strongly predicted patient survival.

Matteo Maria Naldini, Gabriele Casirati, Matteo Barcella, Paola Maria Vittoria Rancoita, Andrea Cosentino, Carolina Caserta, Francesca Pavesi, Erika Zonari, Giacomo Desantis, Diego Gilioli, Matteo Giovanni Carrabba, Luca Vago, Massimo Bernardi, Raffaella Di Micco, Clelia Di Serio, Ivan Merelli, Monica Volpin, Eugenio Montini, Fabio Ciceri, Bernhard Gentner