Related Experiment Video
Updated: May 24, 2026
Murine Model of Leukemia Relapse to Induction Chemotherapy for Acute Lymphoblastic Leukemia
Published on: October 17, 2025
Leukemia-initiating cells of patient-derived acute lymphoblastic leukemia xenografts are sensitive toward TRAIL
Catarina Castro Alves1, Nadia Terziyska, Michaela Grunert
1Department of Gene Vectors, Helmholtz Zentrum München, German Research Center for Environmental Health, Marchioninistrasse 25, Munich, Germany.
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.
Insights
TNF-related apoptosis-inducing ligand (TRAIL) targets leukemia-initiating cells in precursor B-cell acute lymphoblastic leukemia (pre-B ALL). This suggests TRAIL is a promising drug candidate for treating ALL by targeting cancer stem cells.
Area of Science:
- Oncology
- Immunology
- Hematology
Background:
- Cancer stem cells are critical targets for effective antitumor therapies.
- TNF-related apoptosis-inducing ligand (TRAIL) is a potential anticancer agent, but its efficacy against cancer stem cells, particularly leukemia-initiating cells, is not well understood.
Purpose of the Study:
- To investigate whether TRAIL effectively targets leukemia-initiating cells in precursor B-cell acute lymphoblastic leukemia (pre-B ALL).
Main Methods:
- Utilized limiting dilution transplantation assays in NSG mice with patient-derived pre-B ALL xenografts.
- Administered TRAIL treatment both in vitro to xenograft cells and systemically to tumor-bearing mice.
Main Results:
- In vitro TRAIL treatment significantly reduced and delayed xenograft cell engraftment and postponed leukemia progression in mice.
- Systemic TRAIL treatment led to leukemia eradication in 3 out of 5 mice in one patient sample.
Conclusions:
- TRAIL demonstrates efficacy in targeting leukemia-initiating cells derived from pre-B ALL xenografts.
- TRAIL represents a potential therapeutic candidate for acute lymphoblastic leukemia treatment due to its activity against cancer stem cells.
