TNF-related apoptosis-inducing ligand (TRAIL) as a negative regulator of normal human erythropoiesis

Loris Zamai, Paola Secchiero, Sabina Pierpaoli, Alessandra Bassini, Stefano Papa, Emad S. Alnemri, Lia Guidotti, Marco Vitale, Giorgio Zauli

Research output: Contribution to journalArticlepeer-review


The impact of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on normal hematopoietic development was investigated using adult peripheral blood CD34+ hematopoietic progenitor cells, induced to differentiate along the erythroid, megakaryocytic, granulocytic, and monocytic lineages by the addition of specific cytokine cocktails. TRAIL selectively reduced the number of erythroblasts, showing intermediate levels of glycophorin A (glycophorin A(interm)) surface expression, which appeared in liquid cultures supplemented with stem cell factor + interleukin 3 + erythropoietin at days 7-10. However, neither immature (day 4) glycophorin A(dim) erythroid cells nor mature (day 14) glycophorin A(bright) erythroblasts were sensitive to TRAIL-mediated apoptosis. Moreover, pre- exposure to TRAIL significantly decreased the number and size of erythroid colonies in semisolid assays. These adverse effects of TRAIL were selective for erythropoiesis, as TRAIL did not significantly influence the survival of cells differentiating along the megakaryocytic, granulocytic, or monocytic lineages. Furthermore, TRAIL was detected by Western blot analysis in lysates obtained from normal bone marrow mononuclear cells. These findings indicate that TRAIL acts in a lineage- and stage of differentiation-specific manner, as a negative regulator of normal erythropoiesis. (C) 2000 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)3716-3724
Number of pages9
Issue number12
Publication statusPublished - Jun 15 2000

ASJC Scopus subject areas

  • Hematology


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