TRAIL is a potent inducer of apoptosis in myeloma cells derived from multiple myeloma patients and is not cytotoxic to hematopoietic stem cells

Leukemia. 1999 Nov;13(11):1817-24. doi: 10.1038/sj.leu.2401501.

Abstract

TRAIL, the ligand for the newly discovered DR-4 and DR-5 receptor, is a member of the TNF family of death signal transduction proteins with a mechanism of cell death similar to that of Fas and Fas ligand (Fas-L) system. We provide first time evidence that TRAIL is a potent inducer of apoptosis in multiple myeloma (MM) cell lines. TRAIL effectively induced extensive apoptosis in 8226 and ARP-1 MM cells in a time- and dose-dependent manner. Apoptosis with TRAIL reached about 80% within 48 h of treatment with a dose of 160 ng/ml. Furthermore, we provide first time evidence that similar to Fas, TRAIL-induced apoptosis is not blocked by bcl-2 in MM cell lines. Most importantly, TRAIL induced substantial apoptosis in freshly isolated, flow-sorted myeloma cells obtained from different MM patients expressing variable levels of bcl-2. Finally, we demonstrate for the first time that TRAIL is not cytotoxic to purified CD34+/CD45dim hematopoietic stem cells and does not inhibit CFU-GM or BFU-E colony formation in methylcellulose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Antigens, CD*
  • Antigens, CD34 / analysis
  • Antigens, Differentiation / analysis
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins
  • Cell Division / drug effects
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Genes, bcl-2 / genetics
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology
  • Humans
  • Leukocyte Common Antigens / analysis
  • Membrane Glycoproteins / pharmacology*
  • Methylcellulose / metabolism
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology*
  • NAD+ Nucleosidase / analysis
  • Paclitaxel / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • TNF-Related Apoptosis-Inducing Ligand
  • Time Factors
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Antigens, CD
  • Antigens, CD34
  • Antigens, Differentiation
  • Apoptosis Regulatory Proteins
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Methylcellulose
  • Leukocyte Common Antigens
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • NAD+ Nucleosidase
  • ADP-ribosyl Cyclase 1
  • Paclitaxel