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Apoptosis

TRAIL (Apo2L) suppresses growth of primary human leukemia and myelodysplasia progenitors

Leukemia volume 16, pages 67–73 (2002)Cite this article

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, APO2L) has been shown to induce apoptosis in a number of tumor cell lines as well as in some primary tumors whereas cells from most normal tissues are highly resistant to TRAIL-induced apoptosis. We have studied the susceptibility of primary malignant and normal bone marrow hematopoietic progenitors to TRAIL-induced apoptosis. Extracellular domain of human TRAIL with N-terminal His6 tag (His-TRAIL, amino acids 95–281) was produced in E. coli and its apoptosis-inducing ability was compared with the leucine-zipper containing TRAIL, LZ-TRAIL. Both variants of TRAIL had the same apoptosis-inducing ability. Clonogenic progenitor assays showed that His-TRAIL significantly reduced the number of myeloid colonies (CFU-GM) and clusters from patients with acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndromes (MDS). His-TRAIL had no negative effect on the number of CFU-GM colonies and clusters derived from bone marrow cells of AML patients in complete remission, and lymphoma patients without bone marrow involvement, as well as those derived from normal cord blood cells. Moreover, we found that normal human stem cells treated with high doses of His-TRAIL maintain a repopulating potential when transplanted into NOD/SCID mice. To conclude, our data document that TRAIL does not affect normal human hematopoiesis but suppresses the growth of early primary leukemia and myelodysplasia progenitors.

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Acknowledgements

We would like to thank Dr K Michalova for providing us with clinical cytogenetic data of the patients’ cells. We also would like to thank E Mikulova, E Podzimkova, B Krasna, D Singerova and D Dyrova for outstanding technical assistance. We also thank Dr David Lynch (Immunex) for providing us with the recombinant human LZ-TRAIL. The work was supported by grants from the Grant Agency of the Academy of Sciences of the Czech Republic (A5052001), from the Internal Granting Agency of the Czech Ministry of Health (NE/6689-3), from the Grant Agency of the Czech Republic (301/00/1061, 301/99/0350), and from the Grant Agency of the Ministry of Education, Czech Republic No. VZ111100003.

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Author notes

  1. L Andera and T Stopka: The last two authors are the senior co-authors

Authors and Affiliations

  1. Institute of Hematology and Blood Transfusion, Prague, Czech Republic

    M Plasilova, J Jelinek, J Cermak & T Stopka

  2. Department of Pathophysiology, First Medical Faculty, Charles University, Prague, Czech Republic

    J Zivny, E Necas & T Stopka

  3. General Faculty Hospital, Prague, Czech Republic

    R Neuwirtova

  4. Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic

    L Andera

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  1. M Plasilova
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Correspondence to T Stopka.

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Plasilova, M., Zivny, J., Jelinek, J. et al. TRAIL (Apo2L) suppresses growth of primary human leukemia and myelodysplasia progenitors. Leukemia 16, 67–73 (2002). https://doi.org/10.1038/sj.leu.2402338

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