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Titolo:
Histone deacetylase inhibitors induce caspase-dependent apoptosis and downregulation of daxx in acute promyelocytic leukaemia with t(15;17)
Autore:
Amin, HM; Saeed, S; Alkan, S;
Indirizzi:
Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA Loyola Univ Maywood IL USA 60153 Ctr, Dept Pathol, Maywood, IL 60153 USA
Titolo Testata:
BRITISH JOURNAL OF HAEMATOLOGY
fascicolo: 2, volume: 115, anno: 2001,
pagine: 287 - 297
SICI:
0007-1048(200111)115:2<287:HDIICA>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
SUBEROYLANILIDE HYDROXAMIC ACID; TRANSFORMED-CELL DIFFERENTIATION; RETINOIC ACID; SODIUM-BUTYRATE; LEUKEMIA-CELLS; KINASE ACTIVATION; RAR-ALPHA; C-JUN; EXPRESSION; DEATH;
Keywords:
acute promyelocytic leukaemia; apoptosis; historic deacetylase inhibitors; caspases; daxx;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Alkan, S Loyola Univ, Med Ctr, Dept Pathol, 2160 S 1st Ave, Maywood, IL 60153 USA Loyola Univ 2160 S 1st Ave Maywood IL USA 60153 ood, IL 60153 USA
Citazione:
H.M. Amin et al., "Histone deacetylase inhibitors induce caspase-dependent apoptosis and downregulation of daxx in acute promyelocytic leukaemia with t(15;17)", BR J HAEM, 115(2), 2001, pp. 287-297

Abstract

Historic deacetylase (HDAC) appears to play an important role in the pathogenesis of acute promyelocytic leukaemia (APL) as it is recruited by both PML-RAR alpha and PLZF/RAR alpha in leukaemic cells with t(15:17) and t(11:17) respectively. Recent studies have demonstrated that HDAC inhibitors can be therapeutically used in various neoplastic disorders including APL. Celldifferentiation was considered the major mechanism of the anti-leukaemic effects of HDAC inhibitors in APL. However. most of these studies either evaluated the effect of HDAC inhibitors in combination with all-trans retinoicacid (ATRA) or focused on the less common form of APL with t(11;17). To investigate the cellular effects of HDAC inhibitors, including sodium butyrate, trichostatin A, and suberoylanilide hydroxamic acid (SAHA), we used two APL cell lines, NB4 and the ATRA-resistant derivative NB4.306. Moreover, primary cells from five patients with cytogenetic evidence for t(15;17) were also studied. Our results demonstrated that HDAC inhibitors induce distinctcaspase-dependent apoptosis in APL, which showed both concentration-and time-dependence. In addition. changes in the apoptosis-regulatory proteins, daxx, bcl-2 and bax were analysed. HDAC inhibitors induced downregulation ofdaxx. but no significant changes were detected in bcl-2 or bax. In conclusion, apoptosis induced by HDAC inhibitors in APL could provide an effectivestrategy for treatment of patients with t(15;17).

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/05/20 alle ore 04:59:54