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-RARalpha fusion protein, results in more rapid or more sustained cell death. In this model cell line, the authors demonstrate that TGFbeta1, 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 TGFbeta1 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- FLIP(L) and Mcl-1 proteins that are likely to be involved in the suppression of caspase-8 activation and apoptosis.
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Authors | Enrico Garattini, Mineko Terao |
Journal | Leukemia research
(Leuk Res)
Vol. 30
Issue 5
Pg. 519-20
(May 2006)
ISSN: 0145-2126 [Print] England |
PMID | 16246418
(Publication Type: Comment, Editorial)
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Chemical References |
- Apoptosis Regulatory Proteins
- CASP8 and FADD-Like Apoptosis Regulating Protein
- CFLAR protein, human
- Intracellular Signaling Peptides and Proteins
- Membrane Glycoproteins
- Myeloid Cell Leukemia Sequence 1 Protein
- Neoplasm Proteins
- Peptide Fragments
- Proto-Oncogene Proteins c-bcl-2
- TNF-Related Apoptosis-Inducing Ligand
- TNFSF10 protein, human
- Transforming Growth Factor beta
- Transforming Growth Factor beta1
- Tumor Necrosis Factor-alpha
- transforming growth factor beta1 (41-65)
- Tretinoin
- CASP8 protein, human
- Caspase 8
- Caspases
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Topics |
- Acute Disease
- Apoptosis
(drug effects)
- Apoptosis Regulatory Proteins
(metabolism, pharmacology)
- CASP8 and FADD-Like Apoptosis Regulating Protein
- Caspase 8
- Caspases
(drug effects, metabolism)
- Cell Differentiation
(drug effects)
- Cell Proliferation
(drug effects)
- Granulocytes
(cytology)
- HL-60 Cells
- Humans
- Intracellular Signaling Peptides and Proteins
(drug effects, metabolism)
- Leukemia, Myeloid, Acute
(metabolism, pathology)
- Membrane Glycoproteins
(metabolism, pharmacology)
- Myeloid Cell Leukemia Sequence 1 Protein
- Neoplasm Proteins
(drug effects, metabolism)
- Peptide Fragments
(pharmacology)
- Proto-Oncogene Proteins c-bcl-2
(drug effects, metabolism)
- TNF-Related Apoptosis-Inducing Ligand
- Transforming Growth Factor beta
(pharmacology)
- Transforming Growth Factor beta1
- Tretinoin
(antagonists & inhibitors, pharmacology)
- Tumor Cells, Cultured
- Tumor Necrosis Factor-alpha
(metabolism, pharmacology)
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