Increased resistance to apoptosis associated with HL-60 myeloid differentiation status.
Anticancer Res
; 14(5A): 2063-72, 1994.
Article
en En
| MEDLINE
| ID: mdl-7847852
Morphologically HL-60 leukaemia cells largely resemble promyelocytes and can be induced to terminally differentiate in vitro. Upon reaching terminal maturation these cells rapidly undergo apoptosis. Using three chemotherapeutic agents with known apoptosis inducing capability, the susceptibility of RA - and PMA - differentiated cultures was monitored by morphological means and flow cytometry. We observed that as cells with morphological characteristics of mature granulocytes/monocytes became more prominent in the populations, there was an increased resistance to apoptosis. The inhibition of the typical internucleosomal DNA fragmentation was confirmed by agarose gel electrophoresis. However, activation of a CA+/Mg+ independent endonuclease in isolated nuclei was not affected. Flow immunocytometry revealed reduced levels of c-myc and bcl-2 oncoproteins in RA and PMA treated cells. These observations suggest that HL-60 derived granulocytes/monocytes become increasingly resistant to the induction of apoptosis and that this resistance is independent of c-myc and bcl-2 expression. Together these results demonstrate that the phenotypic changes associated with RA and PMA induced differentiation, inhibit a critical step in the progression of apoptosis.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leucemia Promielocítica Aguda
/
Apoptosis
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Anticancer Res
Año:
1994
Tipo del documento:
Article
País de afiliación:
Irlanda
Pais de publicación:
Grecia