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Titolo:
COMMON DEFECTS OF DIFFERENT RETINOIC ACID-RESISTANT PROMYELOCYTIC LEUKEMIA-CELLS ARE PERSISTENT TELOMERASE ACTIVITY AND NUCLEAR-BODY DISORGANIZATION
Autore:
NASONBURCHENAL K; MAERZ W; ALBANELL J; ALLOPENNA J; MARTIN P; MOORE MAS; DMITROVSKY E;
Indirizzi:
MEM SLOAN KETTERING CANC CTR,MOL MED LAB,1275 YORK AVE,BOX 305 NEW YORK NY 10021 MEM SLOAN KETTERING CANC CTR,LAB DEV HEMATOPOIESIS NEW YORK NY 10021
Titolo Testata:
Differentiation
fascicolo: 5, volume: 61, anno: 1997,
pagine: 321 - 331
SICI:
0301-4681(1997)61:5<321:CDODRA>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
PML-RAR-ALPHA; INDUCED GRANULOCYTIC DIFFERENTIATION; EMBRYONAL CARCINOMA-CELLS; RAPID COLORIMETRIC ASSAY; HUMAN MYELOID CELLS; T(15-17) TRANSLOCATION; GROWTH SUPPRESSION; RECEPTOR FUSION; IMMORTAL CELLS; NB4 CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
48
Recensione:
Indirizzi per estratti:
Citazione:
K. Nasonburchenal et al., "COMMON DEFECTS OF DIFFERENT RETINOIC ACID-RESISTANT PROMYELOCYTIC LEUKEMIA-CELLS ARE PERSISTENT TELOMERASE ACTIVITY AND NUCLEAR-BODY DISORGANIZATION", Differentiation, 61(5), 1997, pp. 321-331

Abstract

The acute promyelocytic leukemia (APL) t(15;17) rearrangement fuses the promyelocytic leukemia (PML) gene to the retinoic acid receptor-alpha (RAR alpha). There is expression of the chimeric transcript, PML/RAR alpha, in these APL cells. These clinical APL cases respond to the differentiation agent all-trans retinoic acid (ATRA) with complete but not durable remissions because ATRA resistance develops. The NB4 APL cell line expresses PML/RAR alpha and responds to the growth inhibitoryand differentiation-inducing signals of ATRA. To identify mechanisms responsible for ATRA resistance in APL, ATRA-resistant NB4 cell lines were derived from parental NB4 cells using different strategies. Theselines were resistant to the growth inhibition and differentiation effects of:ATRA. ATRA-resistant cells were isolated as a de novo resistant line from parental NB4 cells (NB4-R1), following chemical mutagenization and selection in ATRA (NB4-R2). or after chronic selection in ATRA (NB4-R3). Common defects linked to this ATRA resistance were found. When cultured in ATRA, these resistant cells still express PML, RAR alpha, and PML/RAR alpha proteins. Sequence abnormalities were not detected in the RAR alpha DNA binding domains cloned from a representative RA-resistant NB4 line. In ATRA-sensitive but not ATRA-resistant NB4 cells, ATRA down-regulated retinoid X receptor-alpha (RXR alpha) expression, a known marker of ATRA response in parental NB4 cells. Notably, engineered overexpression of RXR alpha in ATRA-sensitive NB4 cells did not block ATRA-mediated growth suppression. ATRA treatment of these resistant NB4 lines did not signal a decline in telomerase activity or reorganization of PML-associated nuclear bodies, but both events occurred in ATRA-sensitive NB4 cells. These ATRA-resistant NB4 lines are notfully differentiation-defective, since monocytic maturation was induced following treatment with phorbol 12-myristate 13-acetate (PMA) and 1,25 dihydroxy vitamin D3 (vitamin D3). Notably, induced monocytic differentiation of these distinct ATRA-resistant APL lines markedly repressed telomerase activity. Thus, this study suggests that persistent telomerase activity and nuclear body disorganization are linked to ATRA resistance in APL.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 00:11:16