Granulocytic maturation in cultures of acute myeloid leukemia is not always accompanied by increased apoptosis

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Abstract

In this issue of the Journal, Soucek et al. challenge the assumption that increased functional granulocytic maturation of HL-60, an ATRA-responsive acute myeloid leukemia cell line devoid of the APL-specific PML-RARα fusion protein, results in more rapid or more sustained cell death. In this model cell line, the authors demonstrate that TGFβ1, a well-known haemopoietic growth factor, enhances retinoid-dependent cyto-differentiation and growth arrest while inhibiting apoptosis. Concomitantly, treatment of HL-60 cells with the combination of TGFβ1 and the retinoid partially suppresses ATRA-dependent induction of TRAIL. This is a death receptor ligand of the TNF family implicated in the paracrine mechanism underlying the apoptotic action of ATRA in APL blasts The protein activates the death-receptor-dependent or extrinsic apoptotic pathway, which is associated with caspase-8 activation. Down-regulation of TRAIL is correlated to an increase in the levels of the anti-apoptotic c-FLIPL and Mcl-1 proteins that are likely to be involved in the suppression of caspase-8 activation and apoptosis.

Original languageEnglish
Pages (from-to)519-520
Number of pages2
JournalLeukemia Research
Volume30
Issue number5
DOIs
Publication statusPublished - May 2006

Keywords

  • Apoptosis
  • Granulocytic differentiation
  • Retinoic acid

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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