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

Y. Gazitt

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

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+/CD45(dim) hematopoietic stem cells and does not inhibit CFU-GM or BFU-E colony formation in methylcellulose.

Original languageEnglish (US)
Pages (from-to)1817-1824
Number of pages8
JournalLeukemia
Volume13
Issue number11
DOIs
StatePublished - 1999

Keywords

  • Apoptosis
  • bcl-2
  • Myeloma
  • TRAIL

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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