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

The kiss of death: promises and failures of death receptors and ligands in cancer therapy

“…It has also been observed that recombinant TRAIL induces apoptosis in normal living brain slices and erythropoietic cells, 119,120 while another report claims that CFU-GM or BFU-E colony formation in vitro is unaffected by TRAIL. 121 In the brain, the susceptible cells were identified as neurons, oligodendrocytes, astrocytes and microglial cells. 119 Altogether, the current data suggest that a potential use of TRAIL in cancer therapy has to be considered with caution and awaits further in vivo studies.…”

Regulatory functions of TRAIL in hematopoietic progenitors: human umbilical cord blood and murine bone marrow transplantation

“…24 Consistently, infusion of soluble TRAIL into rodents was not associated with gross abnormalities in hematopoiesis, 25,26 and TRAIL neither induced nor impaired the clonogenic activity of human hematopoietic progenitors in vitro. 22,23 These data argue that TRAIL is not a significant factor in proximal stages of hematopoietic cell differentiation. Nevertheless, administration of recombinant human TRAIL to nonhuman primates resulted in mild anemia, 27 and this pathway is considered to contribute to deficient erythropoiesis in myelodysplastic syndromes.…”

“…[17][18][19] Among the known five TRAIL receptors, DR4 (TRAIL-R1) and DR5 (TRAIL-R2) are associated with transduction of apoptotic signals in humans, 16 whereas mice express only TRAIL-R2. 20,21 Although mRNA encoding TRAIL receptors DR4 and DR5 is frequently detected in CD34 þ progenitors, these cells were insensitive to apoptosis 22,23 even in the presence of low doses of doxorubicin. 24 Consistently, infusion of soluble TRAIL into rodents was not associated with gross abnormalities in hematopoiesis, 25,26 and TRAIL neither induced nor impaired the clonogenic activity of human hematopoietic progenitors in vitro.…”

Modulation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors in a human osteoclast model in vitro

“…TRAIL is capable of inducing apoptosis in myeloma cells both in vitro, making it a solid candidate for therapy (Gazitt, 1999). While malignant plasma cells express TRAIL receptors, there appears to be no relation between TRAIL sensitivity and its pattern of receptor expression (Lincz et al, 2001).…”