TRAIL (Apo2L) suppresses growth of primary human leukemia and myelodysplasia progenitors
Language English Country England, Great Britain Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Acute Disease MeSH
- Colony-Forming Units Assay MeSH
- Apoptosis drug effects MeSH
- Cell Differentiation drug effects MeSH
- K562 Cells drug effects MeSH
- Hematopoietic Stem Cells drug effects MeSH
- HL-60 Cells drug effects MeSH
- Growth Inhibitors pharmacology MeSH
- Jurkat Cells drug effects MeSH
- Cells, Cultured drug effects MeSH
- Leucine Zippers MeSH
- Humans MeSH
- Membrane Glycoproteins chemistry genetics pharmacology MeSH
- Myelodysplastic Syndromes pathology MeSH
- Myeloid Cells drug effects MeSH
- Leukemia, Myeloid pathology MeSH
- Mice, Inbred BALB C MeSH
- Mice, Inbred NOD MeSH
- Mice, SCID MeSH
- Mice MeSH
- Tumor Cells, Cultured drug effects MeSH
- Neoplastic Stem Cells drug effects MeSH
- Lymphoma, Non-Hodgkin pathology MeSH
- Peptide Fragments chemistry genetics pharmacology MeSH
- Graft Survival MeSH
- Antineoplastic Agents pharmacology MeSH
- Recombinant Fusion Proteins chemistry pharmacology MeSH
- Drug Screening Assays, Antitumor MeSH
- Protein Structure, Tertiary MeSH
- Tumor Stem Cell Assay MeSH
- Tumor Necrosis Factor-alpha chemistry genetics pharmacology MeSH
- Hematopoietic Stem Cell Transplantation MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- His-TRAIL protein, recombinant MeSH Browser
- Growth Inhibitors MeSH
- LZ-TRAIL protein, recombinant MeSH Browser
- Membrane Glycoproteins MeSH
- Peptide Fragments MeSH
- Antineoplastic Agents MeSH
- Recombinant Fusion Proteins MeSH
- Tumor Necrosis Factor-alpha MeSH
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 His(6) 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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