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Stem Cell Transplantation

Ex vivo purging of leukemia cells using tumor-necrosis-factor-related apoptosis-inducing ligand in hematopoietic stem cell transplantation

Leukemia volume 17, pages 1375–1383 (2003)Cite this article

Abstract

The aim of this study was to evaluate the potential of tumor-necrosis-factor-related apoptosis-inducing ligand TRAIL to eradicate leukemia cell lines, while sparing normal hematopoietic stem cells. Human Jurkat and Molt-4 cell lines were used to optimize the purging process in umbilical cord blood (UCB) mononuclear cells. The Jurkat cell line was TRAIL sensitive and TRAIL-resistant Molt-4 cell line became sensitive after being treated with TRAIL and a low dose of doxorubicin (0.1 μ M), but UCB mononuclear cells remained resistant. DR4 expression was increased when Jurkat cells were treated with TRAIL, and DR5 expression increased after exposing Molt-4 cells to TRAIL plus a low dose of doxorubicin for 24 h. The expression of DR4 and DR5 in UCB mononuclear cells was unchanged after treatment with TRAIL, a low-dose doxorubicin, or TRAIL plus a low dose of doxorubicin. In TRAIL-sensitive Jurkat cells, caspases 8, 9, 3, and 7 were activated by TRAIL treatment and activation of caspases was augmented by TRAIL plus a low dose of doxorubicin than TRAIL or a low dose of doxorubicin alone in Molt-4 cells. Experiments involving mixture of UCB mononuclear cells and Jurkat or Molt-4 cells showed a marked eradication of leukemia cells and the limiting dilution assay demonstrated an eradication rate of more than 4 logs after 24 h incubation with 100 ng/ml of TRAIL in Jurkat cells. In the case of Molt-4 cells, the eradication rate was about 3 logs when TRAIL was used in combination with a low dose of doxorubicin. No significant decrease in the number of granulocyte–macrophage colony-forming unit) (CFU-GM) colonies was detected when UCB mononuclear cells were treated with TRAIL in combination with a low dose of doxorubicin. These results suggest that TRAIL offers the possibility of being used as an ex vivo purging agent for autologous transplantation in hematologic malignancies.

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Internal Medicine, Soon Chun Hyang University College of Medicine, Seoul, Korea

    N-S Lee, S-E Kim, C-K Kim, K-T Lee, S-K Park, S-H Baick, D-S Hong, H-S Park & J-H Won

  2. Institute for Clinical Molecular Biology Research, Soon Chun Hyang University College of Medicine, Seoul, Korea

    N-S Lee, H-J Cheong, S-J Kim, C-K Kim, K-T Lee, S-K Park, S-H Baick, D-S Hong, H-S Park & J-H Won

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Lee, NS., Cheong, HJ., Kim, SJ. et al. Ex vivo purging of leukemia cells using tumor-necrosis-factor-related apoptosis-inducing ligand in hematopoietic stem cell transplantation. Leukemia 17, 1375–1383 (2003). https://doi.org/10.1038/sj.leu.2402960

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