Together, these data raise the possibility that CALCRL may represent a novel therapeutic target in AML: its expression (i) correlates with chemotherapy resistance; (ii) is high in LSCs, the cell type that needs to be targeted for successful eradication of AML; and (iii) is increased in leukemic over normal hematopoietic stem cells, indicating the existence of a potential therapeutic window. Here, CALCRL is linked to acute myeloid leukemia.