title: Leukemia-initiating cells of patient-derived acute lymphoblastic leukemia xenografts are sensitive toward TRAIL.
abstract: Cancer stem cells represent the most important target cells for antitumor therapy. TRAIL (TNF-related apoptosis-inducing ligand) is a potential anticancer agent that induces apoptosis in a wide variety of tumor cells, but its ability to target cancer stem cells is currently unknown. Here we investigated whether TRAIL targets leukemia-initiating cells. Limiting dilution transplantation assays were performed on xenografts from pediatric patients with precursor B-cell acute lymphoblastic leukemia (pre-B ALL) in NSG mice. In vitro treatment of xenograft cells with TRAIL significantly reduced and delayed their engraftment and procrastinated animal death from leukemia. Systemic TRAIL treatment of mice injected with patient-derived pre-B ALL xenograft cells abrogated leukemia in 3 of 5 mice in 1 sample. In conclusion, our data suggest that TRAIL targets leukemia-initiating cells derived from pre-B ALL xenografts in vitro and in vivo, and hence constitutes an attractive candidate drug for treatment of ALL.
authors.affiliation: Department of Gene Vectors, Helmholtz Zentrum München, German Research Center for Environmental Health, Marchioninistrasse 25, Munich, Germany.
authors.forename: Catarina
authors.initials: C
authors.lastname: Castro Alves
authors.forename: Nadia
authors.initials: N
authors.lastname: Terziyska
authors.forename: Michaela
authors.initials: M
authors.lastname: Grunert
authors.forename: Sibylle
authors.initials: S
authors.lastname: Gündisch
authors.forename: Ulrike
authors.initials: U
authors.lastname: Graubner
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.forename: Irmela
authors.initials: I
authors.lastname: Jeremias
mesh_terms: D000293:Adolescent; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D006085:Graft Survival; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology / Q000637:transplantation; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology / Q000637:transplantation; D023041:Xenograft Model Antitumor Assays
chemical_list: D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human