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Alves, C.C. ; Terziyska, N. ; Grunert, M. ; Gündisch, S. ; Graubner, U.* ; Quintanilla-Martinez, L.* ; Jeremias, I.

Leukemia-initiating cells of patient-derived acute lymphoblastic leukemia xenografts are sensitive toward TRAIL.

Blood 119, 4224-4227 (2012)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords ACUTE MYELOID-LEUKEMIA; STEM-CELLS; B-PRECURSOR; RECEPTOR; APOPTOSIS; EXPRESSION; TRANSPLANTATION; APO2L/TRAIL; RESISTANCE; CANCER
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Journal Blood
Quellenangaben Volume: 119, Issue: 18, Pages: 4224-4227 Article Number: , Supplement: ,
Publisher American Society of Hematology
Reviewing status Peer reviewed