Tumor necrosis factor-related apoptosis-inducing ligand and the regulation of hematopoiesis

Paola Secchiero, Giorgio Zauli

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

PURPOSE OF REVIEW: This review will focus on the emerging role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL-receptors in the pathophysiology of hematopoiesis and on the potential therapeutic applications of either recombinant TRAIL or anti-TRAIL-R1/-R2 agonistic antibodies for the treatment of hematological malignancies. RECENT FINDINGS: While CD34 stem/progenitor cells do not express TRAIL-receptors and are protected from TRAIL-induced apoptosis, accumulating evidence points to a role for elevated expression/release of TRAIL at the bone marrow level in the pathophysiology of aplastic anemia, Fanconi anemia, and myelodysplastic syndromes. In-vitro data show promising synergistic effects of recombinant TRAIL in association with proteasome or histone deacetylase inhibitors, natural compounds or small molecules in the therapy of myeloid and lymphoid malignancies. Moreover, although both recombinant TRAIL and anti-TRAIL-R1/-R2 antibodies are well tolerated in vivo, anti-TRAIL-R1/-R2 agonistic antibodies show the potential advantage of avoiding the neutralizing activity of the soluble receptor osteoprotegerin. SUMMARY: While a chronic pathological elevation of TRAIL at the bone marrow level might contribute to the impairment of normal hematopoiesis, the use of recombinant TRAIL and anti-TRAIL-R1/-R2 agonistic antibodies appears particularly promising for the treatment of hematological malignancies in particular, of multiple myeloma, especially if used in association with innovative therapeutic compounds.

Original languageEnglish
Pages (from-to)42-48
Number of pages7
JournalCurrent Opinion in Hematology
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 2008

Fingerprint

Hematopoiesis
Tumor Necrosis Factor-alpha
TNF-Related Apoptosis-Inducing Ligand Receptors
Apoptosis
Ligands
Antibodies
Hematologic Neoplasms
Stem Cells
Bone Marrow
Fanconi Syndrome
Fanconi Anemia
Osteoprotegerin
Histone Deacetylase Inhibitors
Aplastic Anemia
Myelodysplastic Syndromes
Proteasome Endopeptidase Complex
Multiple Myeloma
Therapeutics
Neoplasms

Keywords

  • Hematological malignancies
  • Hematopoiesis
  • TRAIL
  • TRAIL receptors

ASJC Scopus subject areas

  • Hematology

Cite this

Tumor necrosis factor-related apoptosis-inducing ligand and the regulation of hematopoiesis. / Secchiero, Paola; Zauli, Giorgio.

In: Current Opinion in Hematology, Vol. 15, No. 1, 01.2008, p. 42-48.

Research output: Contribution to journalArticle

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