Invalidation of a novel marker for therapy-resistant leukemic stem cells responsible for relapse in patients and PDX

Drug tolerant leukemic cell stem (LSC) subpopulations may explain frequent relapses in acute myeloid leukemia (AML), suggesting that these Relapse-Initiating Cells (RICs) persistent after chemotherapy represent bona fide targets to prevent drug resistance and relapse. We uncover that the G-protein coupled receptor CALCRL is expressed in RICs, and that the overexpression of CALCRL and/or of its ligand adrenomedullin (ADM) and not CGRP correlates to adverse outcome in AML. CALCRL knockdown impairs leukemic growth, decreases LSC frequency and sensitizes to cytarabine in patient-derived xenograft models. Transfection of MOLM14 cells using genetic approach with shRNA constructs