TY - JOUR
T1 - Granulocytic maturation in cultures of acute myeloid leukemia is not always accompanied by increased apoptosis
AU - Garattini, Enrico
AU - Terao, Mineko
PY - 2006/5
Y1 - 2006/5
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Granulocytic differentiation
KW - Retinoic acid
UR - http://www.scopus.com/inward/record.url?scp=33644851252&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33644851252&partnerID=8YFLogxK
U2 - 10.1016/j.leukres.2005.09.011
DO - 10.1016/j.leukres.2005.09.011
M3 - Article
C2 - 16246418
AN - SCOPUS:33644851252
VL - 30
SP - 519
EP - 520
JO - Leukemia Research
JF - Leukemia Research
SN - 0145-2126
IS - 5
ER -